<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">transplantologiya</journal-id><journal-title-group><journal-title xml:lang="ru">Трансплантология</journal-title><trans-title-group xml:lang="en"><trans-title>Transplantologiya. The Russian Journal of Transplantation</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2074-0506</issn><issn pub-type="epub">2542-0909</issn><publisher><publisher-name>IPO Association of Transplantologists</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.23873/2074-0506-2022-14-2-195-209</article-id><article-id custom-type="elpub" pub-id-type="custom">transplantologiya-657</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОБЗОРНЫЕ СТАТЬИ И ЛЕКЦИИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>REVIEW ARTICLES AND LECTURES</subject></subj-group></article-categories><title-group><article-title>Вектор развития трансплантационной медицины: индукция иммунной толерантности или регуляция иммунного ответа?</article-title><trans-title-group xml:lang="en"><trans-title>The trend for transplant medicine development: induction of immune tolerance or regulation of immune response?</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7079-8383</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кильдюшевский</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Kildyushevsky</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Александр Вадимович Кильдюшевский, проф., д-р мед. наук, ведущий научный сотрудник отделения клинической гематологии и иммунотерапии</p><p>129110, Москва, ул. Щепкина, д. 61/2</p></bio><bio xml:lang="en"><p>Alexandr V. Kildyushevskiy, Prof., Dr. Sci. (Med.), Leading Researcher of the Department of Clinical Hematology and Immunotherapy</p><p>61/2 Shchepkin St., Moscow 129110</p></bio><email xlink:type="simple">kildushev@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0002-9183</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Мойсюк</surname><given-names>Я. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Moysyuk</surname><given-names>Ya. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ян Геннадиевич Мойсюк, проф., д-р мед. наук, руководитель отдела трансплантологии</p><p>129110, Москва, ул. Щепкина, д. 61/2</p></bio><bio xml:lang="en"><p>Yan G. Moysyuk, Prof., Dr. Sci. (Med.), Head of the Department of Transplantology</p><p>61/2 Shchepkin St., Moscow 129110</p></bio><email xlink:type="simple">moysyuktrans@list.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7493-0030</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Митина</surname><given-names>Т. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Mitina</surname><given-names>T. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Татьяна Алексеевна Митина, д-р мед. наук, руководитель отделения клинической гематологии и иммунотерапии</p><p>129110, Москва, ул. Щепкина, д. 61/2</p></bio><bio xml:lang="en"><p>Tatyana A. Mitina, Dr. Sci. (Med.), Director of the Department of Clinical Hematology and Immunotherapy</p><p>61/2 Shchepkin St., Moscow 129110</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-9280-8282</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кофиади</surname><given-names>И. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kofiadi</surname><given-names>I. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Илья Андреевич Кофиади, проф., д-р биол. наук, заведующий лабораторией молекулярной иммуногенетики</p><p>115522, Москва, Каширское ш., д. 24</p></bio><bio xml:lang="en"><p>Ilya A. Kofiadi, Prof., Dr. Sci. (Biol.), Head of Molecular Immunogenetics Laboratory</p><p>24 Kashirskoe Hwy., Moscow 115522</p></bio><email xlink:type="simple">kofiadi@mail.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4393-1759</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Чуксина</surname><given-names>Ю. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Chuksina</surname><given-names>Yu. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Юлия Юрьевна Чуксина, канд. мед. наук, старший научный сотрудник лаборатории биомедицинских методов исследования</p><p>129110, Москва, ул. Щепкина, д. 61/2</p></bio><bio xml:lang="en"><p>Yuliya Yu. Chuksina, Cand. Sci. (Med.), Senior Research Fellow, Biomedical Research Methods Laboratory</p><p>61/2 Shchepkin St., Moscow 129110</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru">ГБУЗ МО МОНИКИ им. М.Ф. Владимирского<country>Россия</country></aff><aff xml:lang="en">Moscow Regional Research and Clinical Institute n.a. M.F. Vladimirskiy<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru">ФГБУ «ГНЦ Институт иммунологии» ФМБА России<country>Россия</country></aff><aff xml:lang="en">National Research Center – Institute of Immunology of the Federal Medical-Biological Agency<country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2022</year></pub-date><pub-date pub-type="epub"><day>14</day><month>06</month><year>2022</year></pub-date><volume>14</volume><issue>2</issue><fpage>195</fpage><lpage>209</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Кильдюшевский А.В., Мойсюк Я.Г., Митина Т.А., Кофиади И.А., Чуксина Ю.Ю., 2022</copyright-statement><copyright-year>2022</copyright-year><copyright-holder xml:lang="ru">Кильдюшевский А.В., Мойсюк Я.Г., Митина Т.А., Кофиади И.А., Чуксина Ю.Ю.</copyright-holder><copyright-holder xml:lang="en">Kildyushevsky A.V., Moysyuk Y.G., Mitina T.A., Kofiadi I.A., Chuksina Y.Y.</copyright-holder><license license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.jtransplantologiya.ru/jour/article/view/657">https://www.jtransplantologiya.ru/jour/article/view/657</self-uri><abstract><p>Одним из величайших достижений медицины за последнее столетие стало внедрение трансплантации органов. Однако, несмотря на значительный потенциал трансплантологии, зачастую являющейся единственным способом терапии тяжелых заболеваний, токсичность иммуносупрессивных препаратов, поддерживающих трансплантат, остается серьезной проблемой для ее дальнейшего развития. Модификация иммунного ответа с целью формирования толерантности к трансплантируемому органу может сыграть важную роль на пути к минимизации иммуносупрессии. Зафиксированные в литературе успешные случаи отмены иммуносупрессивных препаратов по медицинским показаниям при трансплантации почек и печени, а также результаты, полученные в процессе моделирования такой ситуации в эксперименте, доказывают, что достижение толерантности при трансплантации органов принципиально возможно.</p><p>Целью данного обзора является исследование путей иммунологической супрессии и механизмов формирования иммунологической толерантности в области трансплантологии, а также рассмотрение в этой связи последних клинических достижений. В обзоре приведены различные подходы к индукции центральной толерантности при трансплантации солидных органов, реализованные в рамках оригинальных клинических протоколов. Отдельное внимание уделяется новому направлению в трансплантационной медицине – клеточным технологиям, толерогенный эффект которых обеспечивается путем активации периферических механизмов, в частности, за счет активации супрессорной функции регуляторных Т-клеток.</p><p>Мы уделяем отдельное внимание преимуществам и недостаткам этих двух направлений. Какой из них предпочтителен? В каком направлении будет развиваться научная мысль для реализации многолетней цели трансплантологов – избежать отторжения аллотрансплантата без нарушения параметров физиологического гомеостаза организма? Возможные ответы на эти вопросы обсуждены в настоящем обзоре.</p></abstract><trans-abstract xml:lang="en"><p>One of the greatest medical advances of the last century has been the introduction of organ transplantation. However, despite the considerable potential of transplantation as often the only therapy for severe diseases, the toxicity of immunosuppressive drugs supporting the transplant remains a serious problem for its further development. Modification of immune response in order to form tolerance to the transplanted organ can play an important role on the way to minimize immunosuppression. Successful cases of withdrawal of immunosuppressive drugs for medical reasons in kidney and liver transplantation recorded in the literature, as well as the results obtained in the process of modeling such a situation in the experiment, prove that achieving tolerance in organ transplantation is fundamentally possible.</p><p>The aim of this review is to investigate the ways of immunologic suppression and fundamental mechanisms of immunologic tolerance in the field of transplantation and to review the latest clinical achievements in this respect.</p><p>The review describes various approaches to the induction of central tolerance in solid organ transplantation implemented in the framework of the original clinical protocols. Special attention is given to a new direction in transplantation medicine – cell technologies providing tolerogenic effect by means of peripheral mechanisms activation, in particular due to activation of suppressor function of regulatory T cells.</p><p>We draw the attention to the advantages and disadvantages of these two trends. Which of them is preferable? In which direction will scientific thought be developed for realization of the long-term goal of transplantologists: to avoid allograft rejection without affecting the physiological homeostasis of the body? Possible answers to these questions are discussed in this review.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>трансплантация солидных органов</kwd><kwd>иммунная толерантность</kwd><kwd>отторжение трансплантата</kwd><kwd>клеточный химеризм</kwd><kwd>иммуносупрессия</kwd><kwd>регуляторные клетки</kwd><kwd>реакция «трансплантат против хозяина»</kwd></kwd-group><kwd-group xml:lang="en"><kwd>solid organ transplantation</kwd><kwd>immune tolerance</kwd><kwd>graft rejection</kwd><kwd>cell chimerism</kwd><kwd>immunosuppression</kwd><kwd>regulatory cells</kwd><kwd>graft versus host disease</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Ponticelli C. The mechanisms of acute transplant rejection revisited. J Nephrol. 2012;25(2):150–158. PMID: 22101676 https://doi.org/10.5301/jn.5000048</mixed-citation><mixed-citation xml:lang="en">Ponticelli C. The mechanisms of acute transplant rejection revisited. J Nephrol. 2012;25(2):150–158. PMID: 22101676 https://doi.org/10.5301/jn.5000048</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Siu JHY, Surendrakumar V, Richards JA, Pettigrew GJ. T cell allorecognition pathways in solid organ transplantation. Front Immunol. 2018;9:2548. PMID: 30455697 https://doi.org/10.3389/fimmu.2018.02548</mixed-citation><mixed-citation xml:lang="en">Siu JHY, Surendrakumar V, Richards JA, Pettigrew GJ. T cell allorecognition pathways in solid organ transplantation. Front Immunol. 2018;9:2548. PMID: 30455697 https://doi.org/10.3389/fimmu.2018.02548</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Hui E, Cheung J, Zhu J, Su X, Taylor MJ, Wallweber HA, et al. T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition. Science. 2017;355(6332):1428–1433. PMID: 28280247 https://doi.org/10.1126/science.aaf1292</mixed-citation><mixed-citation xml:lang="en">Hui E, Cheung J, Zhu J, Su X, Taylor MJ, Wallweber HA, et al. T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition. Science. 2017;355(6332):1428–1433. PMID: 28280247 https://doi.org/10.1126/science.aaf1292</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Katabathina V, Menias CO, Pick hardt P, Lubner M, Prasad SR. Complications of immunosuppressive therapy in solid organ transplantation. Radiol Clin N Am. 2016;54(2):303–319. PMID: 26896226 https://doi.org/10.1016/j.rcl.2015.09.009</mixed-citation><mixed-citation xml:lang="en">Katabathina V, Menias CO, Pick hardt P, Lubner M, Prasad SR. Complications of immunosuppressive therapy in solid organ transplantation. Radiol Clin N Am. 2016;54(2):303–319. PMID: 26896226 https://doi.org/10.1016/j.rcl.2015.09.009</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Rodr í guez-Per á lvarez M, Ger mani G, Darius T, Lerut J, Tsochatzis E, Burroughs AK. Tacrolimus trough levels, rejection and renal impairment in liver transplantation: a systematic review and meta-analysis. Am J Transplant. 2012;12(10):2797–2814. PMID: 22703529 https://doi.org/10.1111/j.1600-6143.2012.04140.x</mixed-citation><mixed-citation xml:lang="en">Rodr í guez-Per á lvarez M, Ger mani G, Darius T, Lerut J, Tsochatzis E, Burroughs AK. Tacrolimus trough levels, rejection and renal impairment in liver transplantation: a systematic review and meta-analysis. Am J Transplant. 2012;12(10):2797–2814. PMID: 22703529 https://doi.org/10.1111/j.1600-6143.2012.04140.x</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Vajdic CM, van Leeuwen MT. Cancer incidence and risk factors after solid organ transplantation. Int J Cancer. 2009;125(8):1747–1754. PMID: 19444916 https://doi.org/10.1002/ijc.24439</mixed-citation><mixed-citation xml:lang="en">Vajdic CM, van Leeuwen MT. Cancer incidence and risk factors after solid organ transplantation. Int J Cancer. 2009;125(8):1747–1754. PMID: 19444916 https://doi.org/10.1002/ijc.24439</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Lee HH, Joung JY, Kim SH. The effect of subsequent immunosuppressant use in organ-transplanted patients on prostate cancer incidence: a retrospective analysis using the Korean National Health Insurance Database. BMC Urol. 2021;21(1):112. PMID: 28457708 https://doi.org/10.1186/s12894-021-00883-8</mixed-citation><mixed-citation xml:lang="en">Lee HH, Joung JY, Kim SH. The effect of subsequent immunosuppressant use in organ-transplanted patients on prostate cancer incidence: a retrospective analysis using the Korean National Health Insurance Database. BMC Urol. 2021;21(1):112. PMID: 28457708 https://doi.org/10.1186/s12894-021-00883-8</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Engels E.A, Pfeiffer RM, Fraumeni JF, Kasiske BL, Israni AK, Snyder JJ, et al. Spectrum of cancer risk among US solid organ transplant recipients. JAMA. 2011;306(17):1891–1901. PMID: 22045767 https://doi.org/10.1001/jama.2011.1592</mixed-citation><mixed-citation xml:lang="en">Engels E.A, Pfeiffer RM, Fraumeni JF, Kasiske BL, Israni AK, Snyder JJ, et al. Spectrum of cancer risk among US solid organ transplant recipients. JAMA. 2011;306(17):1891–1901. PMID: 22045767 https://doi.org/10.1001/jama.2011.1592</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Collett D, Mumford L, Banner NR, Neuberger J, Watson C. Compari son of the incidence of malignancy in recipients of different types of organs: a UK Registry audit. Am J Trans plant. 2010;10(8):1889–1896. PMID: 20659094 https://doi.org/10.1111/j.1600-6143.2010.03181.x</mixed-citation><mixed-citation xml:lang="en">Collett D, Mumford L, Banner NR, Neuberger J, Watson C. Compari son of the incidence of malignancy in recipients of different types of organs: a UK Registry audit. Am J Trans plant. 2010;10(8):1889–1896. PMID: 20659094 https://doi.org/10.1111/j.1600-6143.2010.03181.x</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Imamura R, Nakazawa S, Yamanaka K, Kakuta Y, Tsutahara K, Taniguchi A, et al. Cumulative cancer incidence and mortality after kidney transplantation in Japan: a long-term multicenter cohort study. Cancer Med. 2021;10(7):2205–2215. PMID: 3331470 https://doi.org/10.1002/cam4.3636</mixed-citation><mixed-citation xml:lang="en">Imamura R, Nakazawa S, Yamanaka K, Kakuta Y, Tsutahara K, Taniguchi A, et al. Cumulative cancer incidence and mortality after kidney transplantation in Japan: a long-term multicenter cohort study. Cancer Med. 2021;10(7):2205–2215. PMID: 3331470 https://doi.org/10.1002/cam4.3636</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Grulich AE, van Leeuwen MT, Falster MO, Vajdic CM. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet. 2007;370(9581):59–67. PMID: 17617273 https://doi.org/10.1016/S0140-6736(07)61050-2</mixed-citation><mixed-citation xml:lang="en">Grulich AE, van Leeuwen MT, Falster MO, Vajdic CM. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet. 2007;370(9581):59–67. PMID: 17617273 https://doi.org/10.1016/S0140-6736(07)61050-2</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Karami S, Yanik EL, Moore LE, Pfeiffer RM, Copeland G, Gonsalves L, et al. Risk of renal cell carcinoma among kidney transplant recipients in the United States. Am J Transplant. 2016;16(12):3479–3489. PMID: 27160653 https://doi.org/10.1111/ajt.13862</mixed-citation><mixed-citation xml:lang="en">Karami S, Yanik EL, Moore LE, Pfeiffer RM, Copeland G, Gonsalves L, et al. Risk of renal cell carcinoma among kidney transplant recipients in the United States. Am J Transplant. 2016;16(12):3479–3489. PMID: 27160653 https://doi.org/10.1111/ajt.13862</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Ojo AO, Held PJ, Port FK, Wolfe RA, Leichtman AB, Young EW, et al. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med. 2003;349(10):931–940. PMID: 12954741 https://doi.org/10.1056/NEJMoa021744</mixed-citation><mixed-citation xml:lang="en">Ojo AO, Held PJ, Port FK, Wolfe RA, Leichtman AB, Young EW, et al. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med. 2003;349(10):931–940. PMID: 12954741 https://doi.org/10.1056/NEJMoa021744</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Levitsky J. Operational tolerance: past lessons and future prospects. Liver Transpl. 2011;17(3):222–32. PMID: 21384504 https://doi.org/10.1002/lt.22265</mixed-citation><mixed-citation xml:lang="en">Levitsky J. Operational tolerance: past lessons and future prospects. Liver Transpl. 2011;17(3):222–32. PMID: 21384504 https://doi.org/10.1002/lt.22265</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Billingham RE, Medawar PB. The technique of free skin grafting in mammals. J Exp Biol. 1951;28(3):385–402. https://doi.org/10.1242/jeb.28.3.385</mixed-citation><mixed-citation xml:lang="en">Billingham RE, Medawar PB. The technique of free skin grafting in mammals. J Exp Biol. 1951;28(3):385–402. https://doi.org/10.1242/jeb.28.3.385</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Owen RD. Immunogenetic con sequences of vascular anastomo ses between bovine twins. Science. 1945;102(2651):400–401. PMID: 17755278 https://doi.org/10.1126/science.102.2651.400</mixed-citation><mixed-citation xml:lang="en">Owen RD. Immunogenetic con sequences of vascular anastomo ses between bovine twins. Science. 1945;102(2651):400–401. PMID: 17755278 https://doi.org/10.1126/science.102.2651.400</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Billingham RE, Brent L, Medawar PB. Actively acquired tolerance of foreign cells. Nature. 1953;172(4379):603–606. PMID: 13099277 https://doi.org/10.1038/172603a0</mixed-citation><mixed-citation xml:lang="en">Billingham RE, Brent L, Medawar PB. Actively acquired tolerance of foreign cells. Nature. 1953;172(4379):603–606. PMID: 13099277 https://doi.org/10.1038/172603a0</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Eder M, Schwarz C, Kammer M, Jacobsen N, Stavroula ML, Cowan MJ, et al. Allograft and patient survival after sequental HSCT and kidney transplantation from the same donor – a multicenter analysis. Am J Transplant. 2019;19(2):475–487. PMID: 29900661 https://doi.org/10.1111/ajt.14970</mixed-citation><mixed-citation xml:lang="en">Eder M, Schwarz C, Kammer M, Jacobsen N, Stavroula ML, Cowan MJ, et al. Allograft and patient survival after sequental HSCT and kidney transplantation from the same donor – a multicenter analysis. Am J Transplant. 2019;19(2):475–487. PMID: 29900661 https://doi.org/10.1111/ajt.14970</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Oura T, Cosimi AB, Kawai T. Chimerism-based tolerance in organ transplantation: preclinical and clinical studies. Clin Exp Immunol. 2017;189(2):190–196. PMID: 28369830 https://doi.org/10.1111/cei.12969</mixed-citation><mixed-citation xml:lang="en">Oura T, Cosimi AB, Kawai T. Chimerism-based tolerance in organ transplantation: preclinical and clinical studies. Clin Exp Immunol. 2017;189(2):190–196. PMID: 28369830 https://doi.org/10.1111/cei.12969</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Kawai T, Cosimi AB, Spitzer TR, Tolkoff-Rubin N, Suthanthiran M, Saidman SL, et al. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2008;24;358(4):353–361. PMID: 18216355 https://doi.org/10.1056/NEJMoa071074</mixed-citation><mixed-citation xml:lang="en">Kawai T, Cosimi AB, Spitzer TR, Tolkoff-Rubin N, Suthanthiran M, Saidman SL, et al. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2008;24;358(4):353–361. PMID: 18216355 https://doi.org/10.1056/NEJMoa071074</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Buhler LH, Spitzer TR, Sykes M, Sachs DH, Delmonico FL, Tolkoff-Rubin N, et al. Induction of kidney allograft tolerance after transient lymphohematopoietic chimerism in patients with multiple myeloma and endstage renal disease. Transplantation. 2002;74(10):1405–1409. PMID: 12451240 https://doi.org/10.1097/00007890-200211270-00011</mixed-citation><mixed-citation xml:lang="en">Buhler LH, Spitzer TR, Sykes M, Sachs DH, Delmonico FL, Tolkoff-Rubin N, et al. Induction of kidney allograft tolerance after transient lymphohematopoietic chimerism in patients with multiple myeloma and endstage renal disease. Transplantation. 2002;74(10):1405–1409. PMID: 12451240 https://doi.org/10.1097/00007890-200211270-00011</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Scandling JD, Busque S, Dejbakhsh-Jones S, Benike C, Millan MT, Shi zuru JA, et al. Tolerance and chimerism after renal and hematopoietic-cell transplantation. N Engl J Med. 2008;358(4):362–368. PMID: 18216356 https://doi.org/10.1056/NEJMoa074191</mixed-citation><mixed-citation xml:lang="en">Scandling JD, Busque S, Dejbakhsh-Jones S, Benike C, Millan MT, Shi zuru JA, et al. Tolerance and chimerism after renal and hematopoietic-cell transplantation. N Engl J Med. 2008;358(4):362–368. PMID: 18216356 https://doi.org/10.1056/NEJMoa074191</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Andreola G, Chittenden M, Shaffer J, Cosimi AB, Kawai T, Cotter P, et al. Mechanisms of donor-specific tolerance in recipients of haploidentical combined bone marrow/kidney transplantation. Am J Transplant. 2011;11(6):1236-1247. PMID: 21645255 https://doi.org/10.1111/j.1600-6143.2011.03566.x</mixed-citation><mixed-citation xml:lang="en">Andreola G, Chittenden M, Shaffer J, Cosimi AB, Kawai T, Cotter P, et al. Mechanisms of donor-specific tolerance in recipients of haploidentical combined bone marrow/kidney transplantation. Am J Transplant. 2011;11(6):1236-1247. PMID: 21645255 https://doi.org/10.1111/j.1600-6143.2011.03566.x</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Colson YL, Li H, Boggs SS, Patrene KD, Johnson PC, Ildstad ST. Durable mixed allogeneic chimerism and tolerance by a nonlethal radiation-based cytoreductive approach. J Immunol. 1996;157(7):2820–2829. PMID: 8816385</mixed-citation><mixed-citation xml:lang="en">Colson YL, Li H, Boggs SS, Patrene KD, Johnson PC, Ildstad ST. Durable mixed allogeneic chimerism and tolerance by a nonlethal radiation-based cytoreductive approach. J Immunol. 1996;157(7):2820–2829. PMID: 8816385</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Sharabi Y, Sachs DH. Mixed chimerism and permanent specific transplantation tolerance induced by a non-lethal preparative regimen. J Exp Med. 1989;169(2):493–502. PMID: 2562984 https://doi.org/10.1084/jem.169.2.493</mixed-citation><mixed-citation xml:lang="en">Sharabi Y, Sachs DH. Mixed chimerism and permanent specific transplantation tolerance induced by a non-lethal preparative regimen. J Exp Med. 1989;169(2):493–502. PMID: 2562984 https://doi.org/10.1084/jem.169.2.493</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Ildstad ST, Sachs DH. Reconstitution with syngeneic plus allogeneic or xenogeneic bone-marrow leads to specific acceptance of allografts or xenografts. Nature. 1984;307(5947):168–70. PMID: 6361574 https://doi.org/10.1038/307168a0</mixed-citation><mixed-citation xml:lang="en">Ildstad ST, Sachs DH. Reconstitution with syngeneic plus allogeneic or xenogeneic bone-marrow leads to specific acceptance of allografts or xenografts. Nature. 1984;307(5947):168–70. PMID: 6361574 https://doi.org/10.1038/307168a0</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Ramakrishnan SK, Page A, Far ris AB 3rd , Singh K, Leopardi F, Hamby K, et al. Evidence for kidney rejection after combined bone marrow and renal transplantation despite ongoing whole-blood chimerism in rhesus macaques. Am J Transplant. 2012;12(7):1755–1764. PMID: 22642491 https://doi.org/10.1111/j.1600-6143.2012.04045.x</mixed-citation><mixed-citation xml:lang="en">Ramakrishnan SK, Page A, Far ris AB 3rd , Singh K, Leopardi F, Hamby K, et al. Evidence for kidney rejection after combined bone marrow and renal transplantation despite ongoing whole-blood chimerism in rhesus macaques. Am J Transplant. 2012;12(7):1755–1764. PMID: 22642491 https://doi.org/10.1111/j.1600-6143.2012.04045.x</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Xu H, Chilton PM, Huang Y, Schanie CL, Yan J, Ildstad ST. Addition of cyclophosphamide to T-cell depletion-based nonmyeloab-lative condi tioning allows donor T-cell engraftment and clonal deletion of alloreactive host T-cells after bone marrow transplantation. Transplantation. 2007;83(7):954–963. PMID: 17460568 https://doi.org/10.1097/01.tp.0000258679.18684.b0</mixed-citation><mixed-citation xml:lang="en">Xu H, Chilton PM, Huang Y, Schanie CL, Yan J, Ildstad ST. Addition of cyclophosphamide to T-cell depletion-based nonmyeloab-lative condi tioning allows donor T-cell engraftment and clonal deletion of alloreactive host T-cells after bone marrow transplantation. Transplantation. 2007;83(7):954–963. PMID: 17460568 https://doi.org/10.1097/01.tp.0000258679.18684.b0</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Umemura A, Morita H, Li XC, Tahan S, Monaco AP, Maki T. Dissociation of hemopoietic chimerism and allograft tolerance after allogeneic bone marrow transplantation. J Immunol. 2001;167(6):3043–3048. PMID: 11544287 https://doi.org/10.4049/jimmunol.167.6.3043</mixed-citation><mixed-citation xml:lang="en">Umemura A, Morita H, Li XC, Tahan S, Monaco AP, Maki T. Dissociation of hemopoietic chimerism and allograft tolerance after allogeneic bone marrow transplantation. J Immunol. 2001;167(6):3043–3048. PMID: 11544287 https://doi.org/10.4049/jimmunol.167.6.3043</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Xu H, Ildstad ST. Transplanta tion: is donor T-cell engraftment a biomarker for tolerance? Nat Rev Nephrol. 2012;8(10):560–561. PMID: 22868709 https://doi.org/10.1038/nrneph.2012.187</mixed-citation><mixed-citation xml:lang="en">Xu H, Ildstad ST. Transplanta tion: is donor T-cell engraftment a biomarker for tolerance? Nat Rev Nephrol. 2012;8(10):560–561. PMID: 22868709 https://doi.org/10.1038/nrneph.2012.187</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Leventhal J, Abecassis M, Miller J, Gallon L, Ravindra K, Tollerud DJ, et al. Chimerism and tolerance without GVHD or engraftment syndrome in HLA-mismatched combined kidney and hematopoietic stem cell transplantation. Sci Transl Med. 2012;4(124):124ra28. PMID: 22399264 https://doi.org/10.1126/scitranslmed.3003509</mixed-citation><mixed-citation xml:lang="en">Leventhal J, Abecassis M, Miller J, Gallon L, Ravindra K, Tollerud DJ, et al. Chimerism and tolerance without GVHD or engraftment syndrome in HLA-mismatched combined kidney and hematopoietic stem cell transplantation. Sci Transl Med. 2012;4(124):124ra28. PMID: 22399264 https://doi.org/10.1126/scitranslmed.3003509</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Niederwieser D, Maris M, Shi zuru JA, Petersdorf E, Hegenbart U, Sandmaier BM, et al. Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with hematological diseases. Blood. 2003;101(4):1620–1629. PMID: 12393457 https://doi.org/10.1182/blood-2002-05-1340</mixed-citation><mixed-citation xml:lang="en">Niederwieser D, Maris M, Shi zuru JA, Petersdorf E, Hegenbart U, Sandmaier BM, et al. Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with hematological diseases. Blood. 2003;101(4):1620–1629. PMID: 12393457 https://doi.org/10.1182/blood-2002-05-1340</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Jochum C, Beste M, Zellmer E, Graves SS, Storb R. CD154 bloc kade and donor-specific transfusions in DLA-identical marrow transplanta tion in dogs conditioned with 1-Gy total body irradiation. Biol Blood Marrow Transplant. 2007;13(2):164–171. PMID: 17241922 https://doi.org/10.1016/j.bbmt.2006.10.031</mixed-citation><mixed-citation xml:lang="en">Jochum C, Beste M, Zellmer E, Graves SS, Storb R. CD154 bloc kade and donor-specific transfusions in DLA-identical marrow transplanta tion in dogs conditioned with 1-Gy total body irradiation. Biol Blood Marrow Transplant. 2007;13(2):164–171. PMID: 17241922 https://doi.org/10.1016/j.bbmt.2006.10.031</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Ozyurek E, Cowan MJ, Koerper MA, Baxter-Lowe LA, Dvorak CC, Horn BN. Increasing mixed chimerism and the risk of graft loss in children undergoing allogeneic hematopoietic stem cell transplantation for non-malignant disorders. Bone Marrow Transplant. 2008;42(2):83–91. PMID: 18391990 https://doi.org/10.1038/BMT.2008.89</mixed-citation><mixed-citation xml:lang="en">Ozyurek E, Cowan MJ, Koerper MA, Baxter-Lowe LA, Dvorak CC, Horn BN. Increasing mixed chimerism and the risk of graft loss in children undergoing allogeneic hematopoietic stem cell transplantation for non-malignant disorders. Bone Marrow Transplant. 2008;42(2):83–91. PMID: 18391990 https://doi.org/10.1038/BMT.2008.89</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Fudaba Y, Spitzer TR, Shaffer J, Kawai T, Fehr T, F Delmonico, et al. Myeloma responses and tolerance following combined kidney and nonmyeloablative marrow transplantation: in vivo and in vitro analyses. Am J Transplant. 2006;6(9):2121–2133. PMID: 16796719 https://doi.org/10.1111/j.1600-6143.2006.01434.x</mixed-citation><mixed-citation xml:lang="en">Fudaba Y, Spitzer TR, Shaffer J, Kawai T, Fehr T, F Delmonico, et al. Myeloma responses and tolerance following combined kidney and nonmyeloablative marrow transplantation: in vivo and in vitro analyses. Am J Transplant. 2006;6(9):2121–2133. PMID: 16796719 https://doi.org/10.1111/j.1600-6143.2006.01434.x</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Scandling JD, Busque S, Shizu ru JA, Lowsky R, Hoppe R, Dejbakhsh-Jones S, et al. Chimerism, graft survival, and withdrawal of immunosuppressive drugs in HLA matched and mismatched patients after living donor kidney and hematopoietic cell transplantation. Am J Transplant. 2015;15(3):695–704. PMID: 25693475 doi 10.1111/ajt.13091</mixed-citation><mixed-citation xml:lang="en">Scandling JD, Busque S, Shizu ru JA, Lowsky R, Hoppe R, Dejbakhsh-Jones S, et al. Chimerism, graft survival, and withdrawal of immunosuppressive drugs in HLA matched and mismatched patients after living donor kidney and hematopoietic cell transplantation. Am J Transplant. 2015;15(3):695–704. PMID: 25693475 doi 10.1111/ajt.13091</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Kawai T, Sachs DH, Sprangers B, Spitzer TR, Saidman SL, Zorn E, et al. Longterm results in recipients of combined HLA-mismatched kidney and bone marrow transplantation without maintenance immunosuppression. Am J Transplant. 2014;14(7):1599–1611. PMID: 24903438 https://doi.org/10.1111/ajt.12731</mixed-citation><mixed-citation xml:lang="en">Kawai T, Sachs DH, Sprangers B, Spitzer TR, Saidman SL, Zorn E, et al. Longterm results in recipients of combined HLA-mismatched kidney and bone marrow transplantation without maintenance immunosuppression. Am J Transplant. 2014;14(7):1599–1611. PMID: 24903438 https://doi.org/10.1111/ajt.12731</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Leventhal JR, Elliott MJ, Yolcu ES, Bozulic LD, Tollerud DJ, Mathew JM, et al. Immune reconstitution/immu nocompetence in recipients of kid ney plus hematopoietic stem/ facilitating cell transplants. Trans plantation. 2015;99(2):288–298. PMID: 25594553 https://doi.org/10.1097/TP.0000000000000605</mixed-citation><mixed-citation xml:lang="en">Leventhal JR, Elliott MJ, Yolcu ES, Bozulic LD, Tollerud DJ, Mathew JM, et al. Immune reconstitution/immu nocompetence in recipients of kid ney plus hematopoietic stem/ facilitating cell transplants. Trans plantation. 2015;99(2):288–298. PMID: 25594553 https://doi.org/10.1097/TP.0000000000000605</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Lee KW, Park JB, Park H, Kwon Y, Lee JS, Kim KS, et al. Inducing transient mixed chimerism for allograft survival without maintenance immunosuppression with combined kidney and bone marrow transplantation: protocol optimization. Transplantation. 2020;104(7):1472-1482. PMID: 31634324 https://doi.org/10.1097/TP.0000000000003006</mixed-citation><mixed-citation xml:lang="en">Lee KW, Park JB, Park H, Kwon Y, Lee JS, Kim KS, et al. Inducing transient mixed chimerism for allograft survival without maintenance immunosuppression with combined kidney and bone marrow transplantation: protocol optimization. Transplantation. 2020;104(7):1472-1482. PMID: 31634324 https://doi.org/10.1097/TP.0000000000003006</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Kohrt HE, Pillai AB, Lowsky R, Strober S. NKT cells, Treg, and their interactions in bone marrow transplantation. Eur J Immunol. 2010;40(7):18621869. PMID: 20583031 https://doi.org/10.1002/eji.201040394</mixed-citation><mixed-citation xml:lang="en">Kohrt HE, Pillai AB, Lowsky R, Strober S. NKT cells, Treg, and their interactions in bone marrow transplantation. Eur J Immunol. 2010;40(7):18621869. PMID: 20583031 https://doi.org/10.1002/eji.201040394</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Leventhal J, Miller J, Abecas sis M, Tollerud DJ, Ildstad ST. Evolving approaches of hematopoietic stem cell-based therapies to induce toler ance to organ transplants: the long road to tolerance. Clin Pharmacol Ther. 2013;93(1):36–45. PMID: 23212110 https://doi.org/10.1038/clpt.2012.201</mixed-citation><mixed-citation xml:lang="en">Leventhal J, Miller J, Abecas sis M, Tollerud DJ, Ildstad ST. Evolving approaches of hematopoietic stem cell-based therapies to induce toler ance to organ transplants: the long road to tolerance. Clin Pharmacol Ther. 2013;93(1):36–45. PMID: 23212110 https://doi.org/10.1038/clpt.2012.201</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Shaw BI, Ord JR, Nobuhara C, Luo X. Cellular therapies in solid organ allotransplantation: promise and pitfalls. Front Immunol. 2021;12:714723. PMID: 34526991 https://doi.org/10.3389/fimmu.2021.714723</mixed-citation><mixed-citation xml:lang="en">Shaw BI, Ord JR, Nobuhara C, Luo X. Cellular therapies in solid organ allotransplantation: promise and pitfalls. Front Immunol. 2021;12:714723. PMID: 34526991 https://doi.org/10.3389/fimmu.2021.714723</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Yang J, Brook MO, CarvalhoGaspar M, Zhang J, Ramon HE, Sayegh MH, et al. Allograft rejection mediated by memory T cells is resistant to regulation. Proc Natl Acad Sci USA. 2007;104(50):19954–19959. PMID: 18042727 https://doi.org/10.1073/pnas.0704397104</mixed-citation><mixed-citation xml:lang="en">Yang J, Brook MO, CarvalhoGaspar M, Zhang J, Ramon HE, Sayegh MH, et al. Allograft rejection mediated by memory T cells is resistant to regulation. Proc Natl Acad Sci USA. 2007;104(50):19954–19959. PMID: 18042727 https://doi.org/10.1073/pnas.0704397104</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Francis RS, Feng G, Tha-In T, Lyons IS, Wood KJ, Bushell A. Induction of transplantation tolerance converts potential effector T cells into graft-protective regulatory T cells. Eur J Immunol. 2011;41(3):726–738. PMID: 21243638 https://doi.org/10.1002/eji.201040509</mixed-citation><mixed-citation xml:lang="en">Francis RS, Feng G, Tha-In T, Lyons IS, Wood KJ, Bushell A. Induction of transplantation tolerance converts potential effector T cells into graft-protective regulatory T cells. Eur J Immunol. 2011;41(3):726–738. PMID: 21243638 https://doi.org/10.1002/eji.201040509</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Wood KJ, Bushell A, Jones ND. Immunologic unresponsiveness to alloantigen in vivo: a role for regulatory T cells. Immunol Rev. 2011;241(1):119–132. PMID: 21488894 https://doi.org/10.1111/j.1600-065X.2011.01013.x</mixed-citation><mixed-citation xml:lang="en">Wood KJ, Bushell A, Jones ND. Immunologic unresponsiveness to alloantigen in vivo: a role for regulatory T cells. Immunol Rev. 2011;241(1):119–132. PMID: 21488894 https://doi.org/10.1111/j.1600-065X.2011.01013.x</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Feng G, Wood KJ, Bushell A. Interferon-gamma conditioning ex vivo generates CD25+ CD62L+ Foxp3+ regulatory T cells that prevent allograft rejection: potential avenues for cellular therapy. Transplantation. 2008;86(4):578–589. PMID: 18724229 https://doi.org/10.1097/TP.0b013e3181806a60</mixed-citation><mixed-citation xml:lang="en">Feng G, Wood KJ, Bushell A. Interferon-gamma conditioning ex vivo generates CD25+ CD62L+ Foxp3+ regulatory T cells that prevent allograft rejection: potential avenues for cellular therapy. Transplantation. 2008;86(4):578–589. PMID: 18724229 https://doi.org/10.1097/TP.0b013e3181806a60</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Page E, Kwun J, Oh B, Knechtle S. Lymphodepletional strategies in transplantation. Cold Spring Harb Perspect Med. 2013;3(7):a015511. PMID: 23818516 https://doi.org/10.1101/cshperspect.a015511</mixed-citation><mixed-citation xml:lang="en">Page E, Kwun J, Oh B, Knechtle S. Lymphodepletional strategies in transplantation. Cold Spring Harb Perspect Med. 2013;3(7):a015511. PMID: 23818516 https://doi.org/10.1101/cshperspect.a015511</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Orlando G, Hematti P, Stratta RJ, Burke GW, Di Cocco P, Pisani F, et al. Clinical operational tolerance after renal transplantation: current status and future challenges. Ann Surg. 2010;252(6):915–928. PMID: 21107102 https://doi.org/10.1097/SLA.0b013e3181f3efb0</mixed-citation><mixed-citation xml:lang="en">Orlando G, Hematti P, Stratta RJ, Burke GW, Di Cocco P, Pisani F, et al. Clinical operational tolerance after renal transplantation: current status and future challenges. Ann Surg. 2010;252(6):915–928. PMID: 21107102 https://doi.org/10.1097/SLA.0b013e3181f3efb0</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Morris H, DeWolf S, Robins H, Sprangers B, LoCascio SA, Shonts BA, et al. Tracking donor-reactive T cells: evidence for clonal deletion in tolerant kidney transplant patients. Sci Transl Med. 2015;7(272):272ra10 PMID: 25632034 https://doi.org/10.1126/sci-translmed.3010760</mixed-citation><mixed-citation xml:lang="en">Morris H, DeWolf S, Robins H, Sprangers B, LoCascio SA, Shonts BA, et al. Tracking donor-reactive T cells: evidence for clonal deletion in tolerant kidney transplant patients. Sci Transl Med. 2015;7(272):272ra10 PMID: 25632034 https://doi.org/10.1126/sci-translmed.3010760</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru">Newell KA, Phippard D, Turka LA. Regulatory cells and cell signatures in clinical transplantation tolerance. Curr Opin Immunol. 2011;23(5):655–659. PMID: 21982510 https://doi.org/10.1016/j.coi.2011.07.008</mixed-citation><mixed-citation xml:lang="en">Newell KA, Phippard D, Turka LA. Regulatory cells and cell signatures in clinical transplantation tolerance. Curr Opin Immunol. 2011;23(5):655–659. PMID: 21982510 https://doi.org/10.1016/j.coi.2011.07.008</mixed-citation></citation-alternatives></ref><ref id="cit51"><label>51</label><citation-alternatives><mixed-citation xml:lang="ru">Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes vari ous autoimmune diseases. J Immunol. 1995;155(3):1151–1164. PMID: 7636184</mixed-citation><mixed-citation xml:lang="en">Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes vari ous autoimmune diseases. J Immunol. 1995;155(3):1151–1164. PMID: 7636184</mixed-citation></citation-alternatives></ref><ref id="cit52"><label>52</label><citation-alternatives><mixed-citation xml:lang="ru">Lin YJ, Hara H, Tai HC, Long C, Tokita D, Yeh P, et al. Suppressive efficacy and proliferative capacity of human regulatory T cells in allogeneic and xenogeneic responses. Transplantation. 2008;86(10):1452–1462. PMID: 19034017 https://doi.org/10.1097/TP.0b013e318188acb0</mixed-citation><mixed-citation xml:lang="en">Lin YJ, Hara H, Tai HC, Long C, Tokita D, Yeh P, et al. Suppressive efficacy and proliferative capacity of human regulatory T cells in allogeneic and xenogeneic responses. Transplantation. 2008;86(10):1452–1462. PMID: 19034017 https://doi.org/10.1097/TP.0b013e318188acb0</mixed-citation></citation-alternatives></ref><ref id="cit53"><label>53</label><citation-alternatives><mixed-citation xml:lang="ru">Veerapathran A, Pidala J, Beato F, Yu XZ, Anasetti C. Ex vivo expansion of human Tregs specific for alloantigens presented directly or indirectly. Blood. 2011;118(20):5671–5680. PMID: 21948174 https://doi.org/10.1182/blood-2011-02-337097</mixed-citation><mixed-citation xml:lang="en">Veerapathran A, Pidala J, Beato F, Yu XZ, Anasetti C. Ex vivo expansion of human Tregs specific for alloantigens presented directly or indirectly. Blood. 2011;118(20):5671–5680. PMID: 21948174 https://doi.org/10.1182/blood-2011-02-337097</mixed-citation></citation-alternatives></ref><ref id="cit54"><label>54</label><citation-alternatives><mixed-citation xml:lang="ru">Schmetterer KG, Neunkirchner A, Pickl WF. Naturally occurring regulatory T cells: markers, mechanisms, and manipulation. FASEB J. 2012;26(6):2253-2276. PMID: 22362896 https://doi.org/10.1096/fj.11-193672</mixed-citation><mixed-citation xml:lang="en">Schmetterer KG, Neunkirchner A, Pickl WF. Naturally occurring regulatory T cells: markers, mechanisms, and manipulation. FASEB J. 2012;26(6):2253-2276. PMID: 22362896 https://doi.org/10.1096/fj.11-193672</mixed-citation></citation-alternatives></ref><ref id="cit55"><label>55</label><citation-alternatives><mixed-citation xml:lang="ru">Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N. Conversion of peripheral CD4+CD25-naive T cells to CD4+CD25+regulatory T cells by TGFbeta induction of transcription factor Foxp3. J Exp Med. 2003;198(12):1875-1886. PMID: 14676299 https://doi.org/10.1084/jem.20030152</mixed-citation><mixed-citation xml:lang="en">Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N. Conversion of peripheral CD4+CD25-naive T cells to CD4+CD25+regulatory T cells by TGFbeta induction of transcription factor Foxp3. J Exp Med. 2003;198(12):1875-1886. PMID: 14676299 https://doi.org/10.1084/jem.20030152</mixed-citation></citation-alternatives></ref><ref id="cit56"><label>56</label><citation-alternatives><mixed-citation xml:lang="ru">Liu W, Putnam AL, Xu-Yu Z, Szot GL, Lee MR, Zhu S, et al. CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ Treg cells. J Exp Med. 2006;203(7):1701-1711. PMID: 16818678 https://doi.org/10.1084/jem.20060772</mixed-citation><mixed-citation xml:lang="en">Liu W, Putnam AL, Xu-Yu Z, Szot GL, Lee MR, Zhu S, et al. CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ Treg cells. J Exp Med. 2006;203(7):1701-1711. PMID: 16818678 https://doi.org/10.1084/jem.20060772</mixed-citation></citation-alternatives></ref><ref id="cit57"><label>57</label><citation-alternatives><mixed-citation xml:lang="ru">Ohkura N, Hamaguchi M, Morikawa H, Sugimura K, Tanaka A, Ito Y, et al. T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and comple mentary events required for Treg cell development. Immunity. 2012;37(5):785–799. PMID: 23123060 https://doi.org/10.1016/j.immuni.2012.09.010</mixed-citation><mixed-citation xml:lang="en">Ohkura N, Hamaguchi M, Morikawa H, Sugimura K, Tanaka A, Ito Y, et al. T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and comple mentary events required for Treg cell development. Immunity. 2012;37(5):785–799. PMID: 23123060 https://doi.org/10.1016/j.immuni.2012.09.010</mixed-citation></citation-alternatives></ref><ref id="cit58"><label>58</label><citation-alternatives><mixed-citation xml:lang="ru">Mantel Py, Ouaked N, Ruckert B, Karagiannidis C, Welz R, Blaser K, et al. Molecular mechanisms underlying FOXP3 induction in human T cells. J Immunol. 2006;176(6):3593–3602. PMID: 16517728 https://doi.org/10.4049/jimmunol.176.6.3593</mixed-citation><mixed-citation xml:lang="en">Mantel Py, Ouaked N, Ruckert B, Karagiannidis C, Welz R, Blaser K, et al. Molecular mechanisms underlying FOXP3 induction in human T cells. J Immunol. 2006;176(6):3593–3602. PMID: 16517728 https://doi.org/10.4049/jimmunol.176.6.3593</mixed-citation></citation-alternatives></ref><ref id="cit59"><label>59</label><citation-alternatives><mixed-citation xml:lang="ru">Shevach EM. Mechanisms of foxp3+ T regulatory cell-mediated suppression. Immunity. 2009;30(5):636–645. PMID: 19464986 https://doi.org/10.1016/j.immuni.2009.04.010</mixed-citation><mixed-citation xml:lang="en">Shevach EM. Mechanisms of foxp3+ T regulatory cell-mediated suppression. Immunity. 2009;30(5):636–645. PMID: 19464986 https://doi.org/10.1016/j.immuni.2009.04.010</mixed-citation></citation-alternatives></ref><ref id="cit60"><label>60</label><citation-alternatives><mixed-citation xml:lang="ru">Li X, Xu H, Huang J, Luo D, Lv S, Lu X, et al. Dysfunctions, molecular mechanisms, and therapeutic strategies of regulatory t cells in rheumatoid arthritis. Front Pharmacol. 2021;12:716081. PMID: 34512345 https://doi.org/10.3389/fphar.2021.716081</mixed-citation><mixed-citation xml:lang="en">Li X, Xu H, Huang J, Luo D, Lv S, Lu X, et al. Dysfunctions, molecular mechanisms, and therapeutic strategies of regulatory t cells in rheumatoid arthritis. Front Pharmacol. 2021;12:716081. PMID: 34512345 https://doi.org/10.3389/fphar.2021.716081</mixed-citation></citation-alternatives></ref><ref id="cit61"><label>61</label><citation-alternatives><mixed-citation xml:lang="ru">Qureshi OS, Zheng Y, Nakamura K, Attridge K, Manzotti C, Schmidt EM, et al. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell extrinsic function of CTLA-4. Science. 2011;332(6029):600–603. PMID: 21474713 https://doi.org/10.1126/science.1202947</mixed-citation><mixed-citation xml:lang="en">Qureshi OS, Zheng Y, Nakamura K, Attridge K, Manzotti C, Schmidt EM, et al. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell extrinsic function of CTLA-4. Science. 2011;332(6029):600–603. PMID: 21474713 https://doi.org/10.1126/science.1202947</mixed-citation></citation-alternatives></ref><ref id="cit62"><label>62</label><citation-alternatives><mixed-citation xml:lang="ru">Pandiyan P, Zheng L, Ishihara S, Reed J, Lenardo MJ. CD4+CD25+Foxp3+ regu latory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nat Immunol. 2007;8(12):1353–1362. PMID: 17982458 https://doi.org/10.1038/ni1536</mixed-citation><mixed-citation xml:lang="en">Pandiyan P, Zheng L, Ishihara S, Reed J, Lenardo MJ. CD4+CD25+Foxp3+ regu latory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nat Immunol. 2007;8(12):1353–1362. PMID: 17982458 https://doi.org/10.1038/ni1536</mixed-citation></citation-alternatives></ref><ref id="cit63"><label>63</label><citation-alternatives><mixed-citation xml:lang="ru">O’Gorman WE, Dooms H, Thorne SH, Kuswanto WF, Simonds EF, Krutzik PO, et al. The initial phase of an immune response functions to activate regulatory T cells. J Immunol. 2009;183(1):332–339. PMID: 19542444 https://doi.org/10.4049/jimmunol.0900691</mixed-citation><mixed-citation xml:lang="en">O’Gorman WE, Dooms H, Thorne SH, Kuswanto WF, Simonds EF, Krutzik PO, et al. The initial phase of an immune response functions to activate regulatory T cells. J Immunol. 2009;183(1):332–339. PMID: 19542444 https://doi.org/10.4049/jimmunol.0900691</mixed-citation></citation-alternatives></ref><ref id="cit64"><label>64</label><citation-alternatives><mixed-citation xml:lang="ru">Mahnke K, Bedke T, Enk AH. Regulatory conversation between antigen presenting cells and regulatory T cells enhance immune suppression. Cell Immunol. 2007;250(1–2):1–13. PMID: 18313653 https://doi.org/10.1016/j.cellimm.2008.01.004</mixed-citation><mixed-citation xml:lang="en">Mahnke K, Bedke T, Enk AH. Regulatory conversation between antigen presenting cells and regulatory T cells enhance immune suppression. Cell Immunol. 2007;250(1–2):1–13. PMID: 18313653 https://doi.org/10.1016/j.cellimm.2008.01.004</mixed-citation></citation-alternatives></ref><ref id="cit65"><label>65</label><citation-alternatives><mixed-citation xml:lang="ru">Syn NL, Teng MW, Mok TS, Soo R.A. De-novo and acquired resistance to immune checkpoint targeting. Lancet Oncol. 2017;18(12):e731–e741. PMID: 29208439 https://doi.org/10.1016/S1470-2045(17)30607-1</mixed-citation><mixed-citation xml:lang="en">Syn NL, Teng MW, Mok TS, Soo R.A. De-novo and acquired resistance to immune checkpoint targeting. Lancet Oncol. 2017;18(12):e731–e741. PMID: 29208439 https://doi.org/10.1016/S1470-2045(17)30607-1</mixed-citation></citation-alternatives></ref><ref id="cit66"><label>66</label><citation-alternatives><mixed-citation xml:lang="ru">Schaier M, Seissler N, Schmitt E, Meuer S, Hug F, Zeier M, et al. DR(high+) CD45RA(–)-Tregs potentially affect the suppressive activity of the total Treg pool in renal transplant patients. PLoS One. 2012;7(3):e34208. PMID: 22470536 https://doi.org/10.1371/journal.pone.0034208</mixed-citation><mixed-citation xml:lang="en">Schaier M, Seissler N, Schmitt E, Meuer S, Hug F, Zeier M, et al. DR(high+) CD45RA(–)-Tregs potentially affect the suppressive activity of the total Treg pool in renal transplant patients. PLoS One. 2012;7(3):e34208. PMID: 22470536 https://doi.org/10.1371/journal.pone.0034208</mixed-citation></citation-alternatives></ref><ref id="cit67"><label>67</label><citation-alternatives><mixed-citation xml:lang="ru">Yamaguchi T, Wing JB, Sakaguchi S. Two modes of immune suppression by Foxp3+ regulatory T cells under inflammatory or non-inflammatory conditions. Semin Immunol. 2011;23(6):424–430. PMID: 22055883 https://doi.org/10.1016/j.smim.2011.10.002</mixed-citation><mixed-citation xml:lang="en">Yamaguchi T, Wing JB, Sakaguchi S. Two modes of immune suppression by Foxp3+ regulatory T cells under inflammatory or non-inflammatory conditions. Semin Immunol. 2011;23(6):424–430. PMID: 22055883 https://doi.org/10.1016/j.smim.2011.10.002</mixed-citation></citation-alternatives></ref><ref id="cit68"><label>68</label><citation-alternatives><mixed-citation xml:lang="ru">Muthukumar T, Dadhania D, Ding R, Snopkowski C, Naqvi R, Lee JB, et al. Messenger RNA for FOXP3 in the urine of renal-allograft recipients. N Engl J Med. 2005;353(22):2342–2351. PMID: 16319383 https://doi.org/10.1056/NEJMoa051907</mixed-citation><mixed-citation xml:lang="en">Muthukumar T, Dadhania D, Ding R, Snopkowski C, Naqvi R, Lee JB, et al. Messenger RNA for FOXP3 in the urine of renal-allograft recipients. N Engl J Med. 2005;353(22):2342–2351. PMID: 16319383 https://doi.org/10.1056/NEJMoa051907</mixed-citation></citation-alternatives></ref><ref id="cit69"><label>69</label><citation-alternatives><mixed-citation xml:lang="ru">Dijke IE, Velthuis JH, Caliskan K, Korevaar SS, Maat AP, Zondervan PE, et al. Intragraft FOXP3 mRNA expression reflects antidonor immune reactivity in cardiac allograft patients. Transplantation. 2007;83(11):1477–1484. PMID: 17565321 https://doi.org/10.1097/01.tp.0000264997.53153.8b</mixed-citation><mixed-citation xml:lang="en">Dijke IE, Velthuis JH, Caliskan K, Korevaar SS, Maat AP, Zondervan PE, et al. Intragraft FOXP3 mRNA expression reflects antidonor immune reactivity in cardiac allograft patients. Transplantation. 2007;83(11):1477–1484. PMID: 17565321 https://doi.org/10.1097/01.tp.0000264997.53153.8b</mixed-citation></citation-alternatives></ref><ref id="cit70"><label>70</label><citation-alternatives><mixed-citation xml:lang="ru">Schaier M, Seissler N, Becker LE, Schaefer SM, Schmitt E, Meuer S, et al. The extent of HLA-DR expression on HLA-DR(+) Tregs allows the identification of patients with clinically relevant borderline rejection. Transpl Int. 2013;26(3):290–299. PMID: 23279010 https://doi.org/10.1111/tri.12032</mixed-citation><mixed-citation xml:lang="en">Schaier M, Seissler N, Becker LE, Schaefer SM, Schmitt E, Meuer S, et al. The extent of HLA-DR expression on HLA-DR(+) Tregs allows the identification of patients with clinically relevant borderline rejection. Transpl Int. 2013;26(3):290–299. PMID: 23279010 https://doi.org/10.1111/tri.12032</mixed-citation></citation-alternatives></ref><ref id="cit71"><label>71</label><citation-alternatives><mixed-citation xml:lang="ru">Collison LW, Chaturvedi V, Henderson AL, Giacomin PR, Guy C, Bankoti J, et al. IL-35-mediated induction of a potent regulatory T cell population. Nat Immunol. 2010;11(12):1093–1101. PMID: 20953201 https://doi.org/10.1038/ni.1952</mixed-citation><mixed-citation xml:lang="en">Collison LW, Chaturvedi V, Henderson AL, Giacomin PR, Guy C, Bankoti J, et al. IL-35-mediated induction of a potent regulatory T cell population. Nat Immunol. 2010;11(12):1093–1101. PMID: 20953201 https://doi.org/10.1038/ni.1952</mixed-citation></citation-alternatives></ref><ref id="cit72"><label>72</label><citation-alternatives><mixed-citation xml:lang="ru">Sullivan JA, AlAdra DP, Olson BM, McNeel DG, Burlingham WJ. Infectious tolerance as seen with 2020 vision: the role of IL-35 and extracellular vesicles. Front Immunol. 2020;11:1867. PMID: 32983104 https://doi.org/10.3389/fimmu.2020.01867</mixed-citation><mixed-citation xml:lang="en">Sullivan JA, AlAdra DP, Olson BM, McNeel DG, Burlingham WJ. Infectious tolerance as seen with 2020 vision: the role of IL-35 and extracellular vesicles. Front Immunol. 2020;11:1867. PMID: 32983104 https://doi.org/10.3389/fimmu.2020.01867</mixed-citation></citation-alternatives></ref><ref id="cit73"><label>73</label><citation-alternatives><mixed-citation xml:lang="ru">Hsu SM, Mathew R, Taylor AW, Stein-Streilein J. Ex-vivo tolerogenic F4/80(+) antigen-presenting cells (APC) induce efferent CD8(+) regulatory T cell-dependent suppression of experimental autoimmune uveitis. Clin Exp Immunol. 2014;176(1):37–48. PMID: 24266626 https://doi.org/10.1111/cei.12243</mixed-citation><mixed-citation xml:lang="en">Hsu SM, Mathew R, Taylor AW, Stein-Streilein J. Ex-vivo tolerogenic F4/80(+) antigen-presenting cells (APC) induce efferent CD8(+) regulatory T cell-dependent suppression of experimental autoimmune uveitis. Clin Exp Immunol. 2014;176(1):37–48. PMID: 24266626 https://doi.org/10.1111/cei.12243</mixed-citation></citation-alternatives></ref><ref id="cit74"><label>74</label><citation-alternatives><mixed-citation xml:lang="ru">Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392(6673):245–252. PMID: 9521319 https://doi.org/10.1038/32588</mixed-citation><mixed-citation xml:lang="en">Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392(6673):245–252. PMID: 9521319 https://doi.org/10.1038/32588</mixed-citation></citation-alternatives></ref><ref id="cit75"><label>75</label><citation-alternatives><mixed-citation xml:lang="ru">Broichhausen C, Riquelme P, Geissler EK, Hutchinson JA. Regulatory macrophages as therapeutic targets and therapeutic agents in solid organ transplantation. Curr Opin Organ Transplant. 2012;17(4):332–342. PMID: 22790067 https://doi.org/10.1097/MOT.0b013e328355a979</mixed-citation><mixed-citation xml:lang="en">Broichhausen C, Riquelme P, Geissler EK, Hutchinson JA. Regulatory macrophages as therapeutic targets and therapeutic agents in solid organ transplantation. Curr Opin Organ Transplant. 2012;17(4):332–342. PMID: 22790067 https://doi.org/10.1097/MOT.0b013e328355a979</mixed-citation></citation-alternatives></ref><ref id="cit76"><label>76</label><citation-alternatives><mixed-citation xml:lang="ru">Hutchinson JA, Geissler EK. Now or never? The case for cell-based immunosuppression in kidney transplantation. Kidney Int. 2015;87(6):1116–1124. PMID: 25738251 https://doi.org/10.1038/ki.2015.50</mixed-citation><mixed-citation xml:lang="en">Hutchinson JA, Geissler EK. Now or never? The case for cell-based immunosuppression in kidney transplantation. Kidney Int. 2015;87(6):1116–1124. PMID: 25738251 https://doi.org/10.1038/ki.2015.50</mixed-citation></citation-alternatives></ref><ref id="cit77"><label>77</label><citation-alternatives><mixed-citation xml:lang="ru">Steinman RM. Decisions about dendritic cells: past, present, and future. Annu Rev Immunol. 2012;30:1–22. PMID: 22136168 https://doi.org/10.1146/annurev-immunol-100311-102839</mixed-citation><mixed-citation xml:lang="en">Steinman RM. Decisions about dendritic cells: past, present, and future. Annu Rev Immunol. 2012;30:1–22. PMID: 22136168 https://doi.org/10.1146/annurev-immunol-100311-102839</mixed-citation></citation-alternatives></ref><ref id="cit78"><label>78</label><citation-alternatives><mixed-citation xml:lang="ru">Andre S, Tough DF, Lacroix-Des mazes S, Kaveri SV, Bayry J. Surveillance of antigen-presenting cells by CD4+ CD25+ regulatory T cells in autoimmunity: immunopathogene sis and therapeutic implications. Am J Pathol. 2009;174(5):1575–1587. PMID: 19349365 https://doi.org/10.2353/ajpath.2009.080987</mixed-citation><mixed-citation xml:lang="en">Andre S, Tough DF, Lacroix-Des mazes S, Kaveri SV, Bayry J. Surveillance of antigen-presenting cells by CD4+ CD25+ regulatory T cells in autoimmunity: immunopathogene sis and therapeutic implications. Am J Pathol. 2009;174(5):1575–1587. PMID: 19349365 https://doi.org/10.2353/ajpath.2009.080987</mixed-citation></citation-alternatives></ref><ref id="cit79"><label>79</label><citation-alternatives><mixed-citation xml:lang="ru">Tang Q, Jeffrey, Bluestone JA. Regulatory T-cell therapy in transplantation: moving to the clinic. Cold Spring Harb Perspect Med. 2013;3(11):a015552. PMID: 24186492 https://doi.org/10.1101/cshperspect.a015552</mixed-citation><mixed-citation xml:lang="en">Tang Q, Jeffrey, Bluestone JA. Regulatory T-cell therapy in transplantation: moving to the clinic. Cold Spring Harb Perspect Med. 2013;3(11):a015552. PMID: 24186492 https://doi.org/10.1101/cshperspect.a015552</mixed-citation></citation-alternatives></ref><ref id="cit80"><label>80</label><citation-alternatives><mixed-citation xml:lang="ru">Oberbauer R, Edinger M, Berlakovich G, Kalhs P, Worel N, Heinze G, et al. A prospective controlled trial to evaluate safety and efficacy of in vitro expanded recipient regulatory T cell therapy and tocilizumab together with donor bone marrow infusion in HLA-mismatched living donor kidney transplant recipi ents (Trex001). Front Med (Lausanne). 2021;7:634260. PMID: 33585521 https://doi.org/10.3389/fmed.2020.634260</mixed-citation><mixed-citation xml:lang="en">Oberbauer R, Edinger M, Berlakovich G, Kalhs P, Worel N, Heinze G, et al. A prospective controlled trial to evaluate safety and efficacy of in vitro expanded recipient regulatory T cell therapy and tocilizumab together with donor bone marrow infusion in HLA-mismatched living donor kidney transplant recipi ents (Trex001). Front Med (Lausanne). 2021;7:634260. PMID: 33585521 https://doi.org/10.3389/fmed.2020.634260</mixed-citation></citation-alternatives></ref><ref id="cit81"><label>81</label><citation-alternatives><mixed-citation xml:lang="ru">Roemhild A, Otto NM, Moll G, Abou-El-Enein M, Kaiser D, Bold G, et al. Regulatory T cells for minimising immune suppression in kidney trans plantation: phase I/IIa clinical trial. BMJ. 2020;371:m3734. PMID: 33087345 https://doi.org/10.1136/bmj.m3734</mixed-citation><mixed-citation xml:lang="en">Roemhild A, Otto NM, Moll G, Abou-El-Enein M, Kaiser D, Bold G, et al. Regulatory T cells for minimising immune suppression in kidney trans plantation: phase I/IIa clinical trial. BMJ. 2020;371:m3734. PMID: 33087345 https://doi.org/10.1136/bmj.m3734</mixed-citation></citation-alternatives></ref><ref id="cit82"><label>82</label><citation-alternatives><mixed-citation xml:lang="ru">Sawitzki B, Harden PN, Reinke P, Moreau A, Hutchinson JA, Game DS, et al. Regulatory cell therapy in kid ney transplantation (The ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials. Lancet. 2020;395(10237):1627-1639. PMID: 32446407 https://doi.org/10.1016/S0140-6736(20)30167-7</mixed-citation><mixed-citation xml:lang="en">Sawitzki B, Harden PN, Reinke P, Moreau A, Hutchinson JA, Game DS, et al. Regulatory cell therapy in kid ney transplantation (The ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials. Lancet. 2020;395(10237):1627-1639. PMID: 32446407 https://doi.org/10.1016/S0140-6736(20)30167-7</mixed-citation></citation-alternatives></ref><ref id="cit83"><label>83</label><citation-alternatives><mixed-citation xml:lang="ru">Sánchez-Fueyo A, Whitehouse G, Grageda N, Cramp ME, Lim TY, Romano M, et al. Applicability, safety, and biological activity of regulatory T cell therapy in liver transplantation. Am J Transplant. 2020;20(4):1125–1136. PMID: 31715056 https://doi.org/10.1111/ajt.15700</mixed-citation><mixed-citation xml:lang="en">Sánchez-Fueyo A, Whitehouse G, Grageda N, Cramp ME, Lim TY, Romano M, et al. Applicability, safety, and biological activity of regulatory T cell therapy in liver transplantation. Am J Transplant. 2020;20(4):1125–1136. PMID: 31715056 https://doi.org/10.1111/ajt.15700</mixed-citation></citation-alternatives></ref><ref id="cit84"><label>84</label><citation-alternatives><mixed-citation xml:lang="ru">Giganti G, Atif M, Mohseni Y, Mastronicola D, Grageda N, Povoleri GA. Treg cell therapy: How cell heterogeneity can make the difference. Eur J Immunol. 2021;51(1):39–55. PMID: 33275279 https://doi.org/10.1002/eji.201948131</mixed-citation><mixed-citation xml:lang="en">Giganti G, Atif M, Mohseni Y, Mastronicola D, Grageda N, Povoleri GA. Treg cell therapy: How cell heterogeneity can make the difference. Eur J Immunol. 2021;51(1):39–55. PMID: 33275279 https://doi.org/10.1002/eji.201948131</mixed-citation></citation-alternatives></ref><ref id="cit85"><label>85</label><citation-alternatives><mixed-citation xml:lang="ru">Attias M, Al-Aubodah T, Piccirillo C. Mechanisms of human FoxP3+ Treg cell development and function in health and disease. Immunol. 2019;197(1):36–51. PMID: 30864147 https://doi.org/10.1111/cei.13290</mixed-citation><mixed-citation xml:lang="en">Attias M, Al-Aubodah T, Piccirillo C. Mechanisms of human FoxP3+ Treg cell development and function in health and disease. Immunol. 2019;197(1):36–51. PMID: 30864147 https://doi.org/10.1111/cei.13290</mixed-citation></citation-alternatives></ref><ref id="cit86"><label>86</label><citation-alternatives><mixed-citation xml:lang="ru">Fritsche E, Volk HD, Reinke P, Abou-El-Enein M. Toward an optimized process for clinical manufacturing of CAR-Treg cell therapy. Trends Bio technol. 2020;38(10):1099–1112. PMID: 31982150 https://doi.org/10.1016/j.tibtech.2019.12.009</mixed-citation><mixed-citation xml:lang="en">Fritsche E, Volk HD, Reinke P, Abou-El-Enein M. Toward an optimized process for clinical manufacturing of CAR-Treg cell therapy. Trends Bio technol. 2020;38(10):1099–1112. PMID: 31982150 https://doi.org/10.1016/j.tibtech.2019.12.009</mixed-citation></citation-alternatives></ref><ref id="cit87"><label>87</label><citation-alternatives><mixed-citation xml:lang="ru">Slomovich S, Bell J, Clerkin KJ, Habal MV, Griffin GM, Raikhelkar JK, et al. Extracorporeal photopheresis and its role in heart transplant rejection: prophylaxis and treatment. Clin Transplant. 2021;35(7):e14333. PMID: 33914369 https://doi.org/10.1111/ctr.14333</mixed-citation><mixed-citation xml:lang="en">Slomovich S, Bell J, Clerkin KJ, Habal MV, Griffin GM, Raikhelkar JK, et al. Extracorporeal photopheresis and its role in heart transplant rejection: prophylaxis and treatment. Clin Transplant. 2021;35(7):e14333. PMID: 33914369 https://doi.org/10.1111/ctr.14333</mixed-citation></citation-alternatives></ref><ref id="cit88"><label>88</label><citation-alternatives><mixed-citation xml:lang="ru">Hachem R, Corris P. Extracorporeal photopheresis for bronchiolitis obliterans syndrome after lung transplantation. Transplantation. 2018;102(7):1059-1065. PMID: 29557913 https://doi.org/10.1097/TP.0000000000002168</mixed-citation><mixed-citation xml:lang="en">Hachem R, Corris P. Extracorporeal photopheresis for bronchiolitis obliterans syndrome after lung transplantation. Transplantation. 2018;102(7):1059-1065. PMID: 29557913 https://doi.org/10.1097/TP.0000000000002168</mixed-citation></citation-alternatives></ref><ref id="cit89"><label>89</label><citation-alternatives><mixed-citation xml:lang="ru">Mazzoni A, Giampietro C, Bianco I, Grazzini T, Nencini C, Pileggi C, et al. Extracorporeal photopheresis and liver transplantation: Our experi ence and preliminary data. Transfus Apher Sci. 2017;56(4):515–519. PMID: 28774829 https://doi.org/10.1016/j.transci.2017.07.008</mixed-citation><mixed-citation xml:lang="en">Mazzoni A, Giampietro C, Bianco I, Grazzini T, Nencini C, Pileggi C, et al. Extracorporeal photopheresis and liver transplantation: Our experi ence and preliminary data. Transfus Apher Sci. 2017;56(4):515–519. PMID: 28774829 https://doi.org/10.1016/j.transci.2017.07.008</mixed-citation></citation-alternatives></ref><ref id="cit90"><label>90</label><citation-alternatives><mixed-citation xml:lang="ru">Kusztal M, Kłak R, Krajewska M, BoratyńskA M, Patrzałek D, Klinger M. Application of extracorporeal photo pheresis in kidney transplant recipi ents: technical considerations and procedure tolerance. Transplant Proc. 2011;43(8):2941–2942. PMID: 21996195 https://doi.org/10.1016/j.transproceed.2011.08.034</mixed-citation><mixed-citation xml:lang="en">Kusztal M, Kłak R, Krajewska M, BoratyńskA M, Patrzałek D, Klinger M. Application of extracorporeal photo pheresis in kidney transplant recipi ents: technical considerations and procedure tolerance. Transplant Proc. 2011;43(8):2941–2942. PMID: 21996195 https://doi.org/10.1016/j.transproceed.2011.08.034</mixed-citation></citation-alternatives></ref><ref id="cit91"><label>91</label><citation-alternatives><mixed-citation xml:lang="ru">Whitehouse G, Gray E, Mastoridis S, Merritt E, Kodela E, Yang JHM, et al. IL-2 therapy restores regulatory T-cell dysfunction induced by calcineurin inhibitors. Proc Natl Acad Sci USA. 2017;114(27):7083–7088. PMID: 28584086 https://doi.org/10.1073/pnas.1620835114</mixed-citation><mixed-citation xml:lang="en">Whitehouse G, Gray E, Mastoridis S, Merritt E, Kodela E, Yang JHM, et al. IL-2 therapy restores regulatory T-cell dysfunction induced by calcineurin inhibitors. Proc Natl Acad Sci USA. 2017;114(27):7083–7088. PMID: 28584086 https://doi.org/10.1073/pnas.1620835114</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
