Естественные киллеры: происхождение, фенотип, функции.

NK-клетки (от Natural killer), или естественные киллеры, представляют собой группу лимфоцитов врожденного иммунитета, образующихся в костном мозге. Выделение NK-клеток в отдельную популяцию лимфоцитов связано с открытием их способности индуцировать гибель опухолевых клеток без предварительной сенсибилизации. В настоящем обзоре предпринята попытка систематизации представленных в литературе многочисленных данных о биологии NK-клеток. Авторами рассмотрены этапы дифференцировки NK-клеток из общего лимфоидного предшественника (CLP) в костном мозге, описаны две функционально различные популяции зрелых NK-клеток – CD56brightCDl6- и CD56dimCD16+. Кроме того, обсуждается роль цитокинов и хемокинов в развитии NK-клеток. В обзоре собраны данные о спектре экспрессируемых NK-клетками адгезионных молекул (LFA-1, LFA-2, LFA-3; αMβ2, αXβ2, L-selectin, VLA-4, VLA-5; PECAM-1; CEACAM-1), цитокиновых рецепторов (IL-1R, IL-2ra, IL-2Rb/IL-2Rc, IL-6Rα, IL-7Ra, IL-8R, IL-10R, IL-12Rβ1, IL-15ra, IL-18R, IL-21ra, IFNGR2, TGFBR, c-Kit, CXCR1, CXCR3, CXCR4, CCR4, CCR5, CCR6, CCR7, IChemR23, CX3CR1), а также рецепторов, регулирующих активность NK-клеток (LILRB1, LILRB2, LILRB4; KIR2DL1-5; KIR2DS1-5; KIR3DL1-3; KIR3DS1; NKG2A, NKG2C, NKG2D; Siglec7, Siglec9; CD16; NKRP-1; TIGIT; TACTILE; NKp30, NKp44, NKp46, NKp80; LAIR-1; PD-1; TIM-3; 2B4; TLR1-9). Авторами также рассмотрены механизмы реализации NK-клетками цитотоксической активности, в том числе за счет экспрессии MHC-I-специфических рецепторов, Fc-рецепторов CD16, взаимодействия рецепторов и лигандов апоптоза (Fas-FasL и TRAIL-TRAILR), а также других рецепторов. В обзоре подробно описано строение иммунологического синапса между NK-клеткой и клеткой-мишенью, рецепторные взаимодействия и роль цитоскелета при его формировании. Помимо активирующего иммунологического синапса, в обзоре описывается ингибирующий вариант, а также приведен пример регуляции активности NK-клеток посредством ингибирующего синапса. Авторами суммированы данные о способах экзоцитоза литических гранул NK-клетками, включающих полное или частичное слияние везикул с плазматической мембраной, экзоцитоз везикул, содержащих перфорин и FasL, и образование микровезикул, содержащих гранзим B. В обзоре описаны данные о способности NK-клеток сохранять активированное состояние в течение продолжительного времени, а также поддерживать контакт одновременно с несколькими мишенями. Помимо функций, свойственных естественным киллерам как клеткам врожденного иммунитета, авторы указывают на их способность проявлять черты клеток адаптивного иммунитета. В целом, разнообразие механизмов, регулирующих активность NK-клеток, дополняет специфические функции лимфоцитов, что делает работу иммунной системы более эффективной.

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