Особенности экспрессии ингибиторных рецепторов на эффекторных и регуляторных Т-клетках в контексте терапии ингибиторами «контрольных точек» иммунного ответа

Ингибиторные рецепторы PD-1, TIM-3, LAG-3 и др. – «контрольные точки» иммунного ответа (immune checkpoint, «чек-пойнт») – экспрессируются активированными эффекторными Т-лимфоцитами с целью ограничения интенсивности иммунного ответа. В условиях хронического инфекционного процесса и при опухолевом росте чек-пойнт-рецепторы экспрессируют Т-клетки в состоянии «истощения» (T cell exhaustion), характеризующемся снижением их пролиферативной, цитотоксической и цитокин-продуцирующей активности. Восстановление функциональной активности Т-клеток лежит в основе механизма действия терапевтических моноклональных антител – «чек-пойнт-ингибиторов», таких как анти-PD-1/PD-L1 и анти-LAG-3, используемые в противоопухолевой терапии. В то же время чек-пойнт-рецепторы экспрессируют многие другие популяции клеток, в том числе регуляторные Т-клетки (Т-рег), супрессирующие реакции иммунного ответа. Данные о функциях ингибиторных рецепторов на Т-рег продолжают изучаться. В настоящей публикации мы приводим современные представления об экспрессии ингибиторных чек-пойнт-рецепторов популяциями Т-рег и их связи с эффектами терапии чек-пойнт-ингибиторами.

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