transplantologiyaТрансплантологияTransplantologiya. The Russian Journal of Transplantation2074-05062542-0909IPO Association of Transplantologists10.23873/2074-0506-2020-12-1-20-27transplantologiya-476Research ArticleАКТУАЛЬНЫЕ ВОПРОСЫ ТРАНСПЛАНТОЛОГИИACTUAL ISSUES OF TRANSPLANTATIONИсследование субпопуляции CD3+ CD4- CD8- даблнегативных Т-лимфоцитов у пациентов после трансплантации почкиResearch of subpopulation CD3+ CD4- CD8- double-negative T lymphocytes in kidney transplant recipientshttps://orcid.org/0000-0003-3061-5324ЗыблеваС. В.ZyblevaS. V.

Светлана Валерьевна Зыблева, канд. мед. наук, врач-иммунолог, ученый секретарь 

Svetlana V. Zybleva, Cand. Med. Sci., Immunologist, Academic Secretary

zyb-svetlana@yandex.ruhttps://orcid.org/0000-0002-0968-6630ЗыблевС. Л.ZyblevS. L.

Сергей Леонидович Зыблев канд. мед. наук, доцент, врач-хирург хирургического отделения (трансплантации, реконструктивной и эндокринной хирургии)

Sergey L. Zyblev Cand. Med. Sci., Associate Professor, Surgeon, Transplantation, Endocrine and Reconstructive Surgery Department

ГУ «Республиканский научно-практический центр радиационной медицины и экологии человека»РоссияRepublican Research Center for Radiation Medicine and Human EcologyRussian Federation2020180320201212027Copyright © Зыблева С.В., Зыблев С.Л., 20202020Зыблева С.В., Зыблев С.Л.Zybleva S.V., Zyblev S.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.jtransplantologiya.ru/jour/article/view/476Введение

Введение. CD3+CD4- CD8- являются одной из субпопуляций T-регуляторных лимфоцитов. Согласно данным литературы, обнаружено увеличение содержания графт-инфильтрирующих CD3+CD4- CD8- в тканях ксенотрансплантата сердца экспериментальной модели с длительной выживаемостью трансплантата. Описана эффективность инфузии CD3+CD4- CD8- с целью индуцирования толерантности трансплантата кожи. Показано также, что снижение уровня CD3+CD4- CD8- в периферической крови у пациентов при трансплантации гемопоэтических стволовых клеток ассоциировалось с развитием реакции трансплантат против хозяина.

Цель исследования

Цель исследования. Изучить изменения показателей CD3+CD4- CD8- даблнегативных Т-лимфоцитов в периферической крови у реципиентов почечного трансплантата.

Материал и методы

Материал и методы. В исследование включены 165 реципиентов, которым выполнена трансплантация почки. Определяли концентрацию в крови креатинина и мочевины перед операцией, на 7-е и 360-е сутки после трансплантации. Содержание CD3+CD4- CD8- лимфоцитов изучали перед операцией, на 3-и, 7-е, 30-е, 90-е, 180-е и 360-е сутки после операции. Ранняя функция трансплантата оценивалась на 7-е сутки после операции. При уровне креатинина ниже 300 мкмоль/л функция считалась первичной. Дисфункция трансплантата считалась установленной при значениях креатинина равных или превышающих 300 мкмоль/л и необходимости в диализе на первой неделе после операции. Удовлетворительная функция трансплантата через год характеризовалась уровнем креатинина в крови ниже 150 мкмоль/л, отсутствием эпизодов отторжения трансплантата и необходимости в диализе на первом году наблюдения. Сформированы четыре группы реципиентов. Первая группа – пациенты с первичной и удовлетворительной поздней функцией трансплантата. Вторая группа – с первичной функцией и поздней дисфункцией трансплантата. Третья группа – с первичной дисфункцией и поздней удовлетворительной функцией. Четвертая группа – с первичной и поздней дисфункцией трансплантата.

Результаты

Результаты. В первой и второй группах статистически значимых различий по уровню CD3+CD4- CD8- в крови в течение года выявлено не было. Через год отмечено статистически значимое снижение содержания CD3+CD4- CD8- в группе с поздней дисфункцией трансплантата. В третьей и четвертой группах была выявлена похожая тенденция. В четвертой группе (с поздней дисфункцией трансплантата) уровень CD3+CD4- CD8- был статистически значимо ниже только через год наблюдения по сравнению с показателем в третьей группе. Отмечены отрицательные корреляционные связи между показателями CD3+CD4- CD8- и уровнем креатинина и мочевины. Таким образом, высокие значения содержания CD3+CD4- CD8- у реципиентов почечного трансплантата через год ассоциировались с удовлетворительной функцией трансплантата.

Выводы

Выводы. 1. Для стабильной годовой удовлетворительной функции почечного трансплантата характерно повышение уровня в крови CD3+CD4- CD8- Т-лимфоцитов. 2. Дисфункция почечного трансплантата в позднем посттрансплантационном периоде характеризуется снижением уровня в крови CD3+CD4- CD8- Т-лимфоцитов.

Авторы заявляют об отсутствии конфликта интересов.

Introduction

Introduction. CD3+CD4- CD8- cells represent one of the subpopulations of T-regulatory lymphocytes. According to literature reports, an increase in the content of graft-infiltrating CD3+CD4- CD8- T cells was detected in the heart xenograft tissues of an experimental model with a long-term graft survival. The efficacy of CD3+CD4- CD8- infusion to induce skin graft tolerance was described. Some studies have shown that a decrease in CD3+CD4- CD8- content in peripheral blood of patients undergoing to hematopoietic stem cell transplantation was associated with the development of a graft-versus-host reaction.

Objectives

Objectives. To study changes in the values of CD3+CD4- CD8- double-negative T lymphocytes in peripheral blood in kidney transplant recipients.

Material and methods

Material and methods. The study included 165 recipients who underwent kidney transplantation. The creatinine and urea concentrations in blood were determined before surgery, on day 7, and day 360 after transplantation. The content of CD3+CD4- CD8- lymphocytes was studied before surgery, on the 3rd, 7th, 30th, 90th, 180th and 360th days after surgery. Early graft function was assessed on day 7 after transplantation. The function was defined as a primary one at creatinine levels below 300 μmol/L. The graft dysfunction was defined as creatinine values equal to or greater than 300 μmol/L and the need for dialysis in the first week after surgery. The satisfactory graft function after a year was characterized by the blood creatinine level below 150 μmol/L, absent episodes of graft rejection, and no need for dialysis in the first year of follow-up. There were 4 groups of recipients formed. The first group included patients with the primary graft function and satisfactory late graft function. The second group included patients with the primary function and late graft dysfunction. The third group included patients with the primary dysfunction and late satisfactory function. The fourth group included patients with the primary and late graft dysfunction.

Results

Results. In the first and second groups, there were no significant differences in the blood level of CD3+CD4- CD8- during the year. After a year, a significant CD3+CD4- CD8- decrease was noted in the group with late graft dysfunction. A similar tendency was revealed in the third and fourth groups. In the fourth group (with late graft dysfunction), the level of CD3+CD4- CD8- was significantly lower only after a year of observation compared with the levels in the third group. A negative correlation was noted between the CD3+CD4- CD8- values and the creatinine and urea levels. Thus, high CD3+CD4- CD8- values in kidney transplant recipients after a year were associated with a satisfactory graft function.

Conclusions

Conclusions. 1. A stable 1-year satisfactory kidney graft function is characterized by an increase in the blood level of CD3+CD4- CD8- T lymphocytes. 2. A kidney graft dysfunction in the late post-transplant period is characterized by a decrease in the blood level of CD3+CD4- CD8- T lymphocytes.

Authors declare no conflict of interest.

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The authors declare that there are no conflicts of interest present.