Роль неканонических Т-клеток в гомеостазе и патологии

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.

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