Abstract
Dendritic cells (DCs) play a key role in maintaining the peripheral tolerance of lymphocytes to autoantigens. Recovery of immunological tolerance in autoimmune diseases, particularly, in rheumatoid arthritis (RA) is considered a new therapeutic strategy. The aim of this work was to study the effect of dexamethasone-modified DCs generated from monocytes of RA patients in the presence of IFNα (DCsDex), upon autologous T lymphocytes in mixed leukocyte culture (auto-MLC), and to investigate possible mechanisms of the DCsdextolerogenic effect upon autoreactive T cells. We have shown, that DCsDexfrom RA patients induce T cell hyporeactivity in auto-MLC. Hyporeactivity of T cells is associated with cell cycle blockage in CD4+T lymphocytes and decreased IFNγ, IL-17, IL-4 and IL-13 production, which indicates the induction of CD4+T cell anergy. In this case, inhibition of Th1/Th17 has been more pronounced than the suppression of Th2 cells producing IL-4 and IL-13. Along with T cell anergy, the decrease of proliferative response in auto-MLC is associated with increased CD3+T lymphocyte apoptosis. In addition, the DCsDexof RA patients suppresses the proliferation of autologous T cells stimulated by unmodified DCs. This effect is associated with enhancement of IL-10-producing CD4+T cells in the auto-MLC, thus being indicative for an ability of DCsDexto induce conversion of CD4+T lymphocytes into regulatory T cells (Tr1). The data obtained characterize a new type of tolerogenic DCs, generated from blood monocytes of RA patients in the presence of IFNα and modified by dexamethasone, thus revealing a mechanism for tolerogenic effect of DCsDexupon T cells that recognize self-antigens in auto-MLC.
Highlights
Влияние ДКдекс на функции аутологичных Т-клеток у больных РА Effect of DCsDex on autologous T cell functions in rheumatoid arthritis (RA) patients тимальных протоколов получения тДК уделяется особое внимание
Data are presented as medians, interquartile and min-max range
PW, the significance of differences of DCsDex compared with DCsC (Wilcoxon Matched Pairs Test)
Summary
ВЛИЯНИЕ ДЕКСАМЕТАЗОН-МОДИФИЦИРОВАННЫХ ДЕНДРИТНЫХ КЛЕТОК, ГЕНЕРИРОВАННЫХ С IFNα, НА ФУНКЦИИ АУТОЛОГИЧНЫХ Т-ЛИМФОЦИТОВ У БОЛЬНЫХ РЕВМАТОИДНЫМ АРТРИТОМ. Курочкина Ю.Д., Тыринова Т.В., Леплина О.Ю., Тихонова М.А., Сизиков А.Э., Сулутьян А.Э., Чумасова О.А., Останин А.А., Черных Е.Р. Установлено, что ДКдекс больных РА индуцируют состояние гипореактивности Т-лимфоцитов в ауто-СКЛ. Данный эффект сопряжен с возрастанием в ауто-СКЛ CD4+Т-клеток, секретирующих IL-10, и свидетельствует о способности ДКдекс индуцировать конверсию CD4+Т-лимфоцитов в регуляторные Т-клетки (Tr1). Полученные данные характеризуют новый тип толерогенных ДК, генерированных из моноцитов крови больных РА в присутствии интерферона-альфа и модифицированных дексаметазоном (ДКдекс ), и раскрывают механизмы толерогенного действия ДКдекс на Т-клетки, распознающие собственные антигены в ауто-СКЛ. Черных «Влияние дексаметазон-модифицированных дендритных клеток, генерированных с IFNα, на функции аутологичных Т-лимфоцитов у больных ревматоидным артритом» // Медицинская иммунология, 2019.
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