mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-RON-2918mimmun-2918Research ArticleОБЗОРЫREVIEWSРоль неканонических Т-клеток в гомеостазе и патологииRole of non-canonical T cells in homeostasis and pathologyТоптыгинаА. П.ToptyginaA. P.

Топтыгина А.П. – д.м.н., главный научный сотрудник, руководитель лаборатории цитокинов; профессор кафедры иммунологии биологического факультета

125212, Россия, Москва, ул. Адмирала Макарова, 10

Тел.: 8 (495) 452-18-01

Факс: 8 (495) 452-18-30

Toptygina A.P., PhD, MD (Medicine), Chief Research Associate, Head, Laboratory of Cytokines; Professor, Department of Immunology, Faculty of Biology

10 Admiral Makarov St Moscow 125212 Russian Federation

Phone: +7 (495) 452-18-01

Fax: +7 (495) 452-18-30

toptyginaanna@rambler.ruФБУН «Московский научно-исследовательский институт эпидемиологии и микробиологии имени Г.Н. Габричевского» Роспотребнадзора; ФГБОУ ВО «Московский государственный университет имени М.В. Ломоносова»РоссияG.N. Gabrichevsky Research Institute for Epidemiology and Microbiology; Lomonosov Moscow State UniversityRussian Federation202429112023263449464Copyright © Топтыгина А.П., 20242024Топтыгина А.П.Toptygina A.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2918

Помимо хорошо известных субпопуляций Т-лимфоциов адаптивного иммунитета и лимфоцитов врожденного иммунитета (innate lymphoid cells) существует промежуточная группа лимфоцитов (innate-like cells), уже обладающая Т-клеточным рецептором, но с ограниченным репертуаром. В эту группу следует отнести γδТ-клетки, субпопуляции NKT-клеток I и II типов, несущих как Т-рецептор, так и рецепторы NK-клеток и mucosal-associated invariant T (MAIT) клетки. Развитие innate-like cells происходит в тимусе, однако положительная и отрицательная селекция их проходит без участия эпителиальных клеток тимуса. Отличительной особенностью является то, что innate-like cells приобретают эффекторный фенотип уже в тимусе, поэтому не требуют сложных реакций активации при распознании антигена. На момент выхода из тимуса неканонические Т-клетки экспрессируют хемокиновые рецепторы, позволяющие им мигрировать в барьерные ткани уже в раннем возрасте. Характерной особенностью Т-клеточного рецептора innate-like cells является распознавание непептидных антигенов, презентированных в неполиморфных молекулах тканевой совместимости (МНС-Ib). К этому типу молекул относятся молекулы CD1 a/b/c/d/e и молекула MR1. Эти молекуклы презентируют липидные, гликолипидные антигены и метаболиты витаминов группы В, синтезируемые различными представителями микробиоты. Наличие функционально различных субпопуляций innate-like cells, имеющих активированный фенотип, позволяют им быстро реагировать на антиген продукцией цитокинов, типичных для Th1, Th2, Th17. Также они обладают цитотоксической и иммунорегуляторной активностью. Эти клетки активно вовлечены в регуляцию гомеостаза барьерных тканей и взаимодействие с микробиотой. Они синтезируют факторы роста для эпителиальных клеток, фибробластов, эндотелия сосудов, что необходимо для регенерации поврежденных тканей. Также они участвуют в противоинфекционной защите, направляя развитие иммунного ответа. Более того, они оказались участниками многих аутоиммунных заболеваний. Особенности функционирования innate-like cells делают их перспективной мишенью для терапевтических воздействий. Показано, что антибиотики, салицилаты и некоторые другие известные препараты оказывают влияние на innate-like cells. Различные варианты диеты также влияют на активность этих клеток.

In addition to the subsets of T lymphocytes and innate lymphocytes (innate lymphoid cells), the well-known players in adaptive immunity, there is an intermediate group of lymphocytes (innate-like cells) that already possess the T cell receptor, but with a restricted repertoire. This group includes γδT cells, subsets of type I and II NKT cells carrying both T cell receptor and NK-cell receptors, and mucosal-associated invariant T (MAIT) cells. The development of innate-like cells occurs in the thymus, but their positive and negative selection takes place without the participation of thymic epithelial cells. A distinctive feature is that innate-like cells acquire an effector phenotype already in the thymus, and therefore do not require complex activation reactions during antigen recognition. Upon exit from the thymus, noncanonical T cells express chemokine receptors, allowing them to migrate into barrier tissues at an early age. A characteristic feature of the T cell receptor innate-like cells is the recognition of non-peptide antigens presented in non-polymorphic histocompatibility molecules (MHC-Ib). This type of molecule includes the CD1 a/b/c/d/e molecule and the MR1 molecule. These molecules present lipid, glycolipid antigens and metabolites of B vitamins, synthesized by various representatives of the microbiota. The presence of functionally different subpopulations of innate-like cells with an activated phenotype allows them to quickly respond to the antigen by producing cytokines typical of Th1, Th2, Th17. They also exhibit cytotoxic and immunoregulatory activity. These cells are actively involved in regulation of barrier tissue homeostasis and interaction with microbiota. They synthesize growth factors for epithelial cells, fibroblasts, and vascular endothelium, which are required for regeneration of damaged tissues. They also participate in anti-infectious defense, directing the development of the immune response. Moreover, they have been found to be involved in many autoimmune diseases. The special functions of innate-like cells make them a promising target for therapeutic interventions. It has been shown that antibiotics, salicylates and some other well-known drugs exert certain effects on the innate-like cells. Different dietary options also affect the activity of these cells.

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