Гамма-дельта (γδ) T-клетки: происхождение, фенотип, функции

Важнейшей функцией γδТ-клеток является контроль за реакциями врожденного и адаптивного иммунитета. Эти клетки также участвуют в противобактериальном, противовирусном, противоопухолевом иммунитете, регулируют воспаление, определяют гомеостаз барьерных тканей, регулируют взаимодействие клеток в зоне маточно-плацентарного контакта и осуществляют надзор за течением беременности, участвуют в патогенезе аутоиммунных заболеваний, участвуют в ранозаживлении, поддерживают целостность эпителия. За последние годы в литературе появилось большое количество данных о многообразии субпопуляций γδT-клеток, порой противоположных, или даже антагонистических, роли этих субпопуляций в физиологических и патологических процессах. Поэтому целью настоящего обзора явилась систематизация данных о биологии γδT-клеток, их происхождении, фенотипе, функциях и способах применения в клинике. В обзоре изложены современные представления о происхождении γδТ-клеток, стадиях их внутритимической дифференцировки, возможностях внетимической трансдифференцировки одних субпопуляций в другие. В обзоре приведена современная классификация субпопуляций γδТ-клеток человека, основанная на экспрессии γ- и δ-цепей Т-клеточного рецептора, описаны фенотип и свойства наиболее распространенных популяций Vδ1, Vδ2, Vδ3 Т-клеток. Приведена классификация γδТ-клеток человека, основанная на продукции ими цитокинов и экспрессии внутриклеточных мессенджеров, подробно описаны свойства и функции наиболее изученных субпопуляций: γδT1, γδT17, γδNKT, γδTreg, γδTAPC, γδTfh. В обзоре особое внимание уделяется фенотипу различных популяций, секреции ими цитокинов, приводятся данные об экспрессии поверхностных рецепторов γδТ-клеток человека и их функциях. В частности, рассмотрены особенности строения и лиганды γδТ-клеточного рецептора, а также рецепторы, контролирующие их активность (LIRB1/ILT2, KIR2DL1, KIR2DL2/3, KIR2DL4, KIR2DS1, KIR2DS2, KIR3DL2, KLRD1, NKG2A, NKG2C, NKG2D, NKG2F, NKp30, NKp44, NKp46, KLRC3, DNAM1, KLRG1/MAFA, FcγRIII, BTLA, PD1, TIGIT, VISTA, LAG3, TIM3, CTLA-4, 2B4, NK1 (NK28), KLRB1, TLR1, TLR2, TLR3, TLR5, TLR6, TLR7, TLR8), цитотоксичность в отношении клеток-мишеней, хемокиновые CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR9, CCR10, CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, цитокиновые и адгезионные рецепторы. В обзоре приведена информация об участии субпопуляций γδТ-клеток человека в различных физиологических и патологических процессах, отмечена их неоднозначная роль в надзоре за опухолевым ростом. На основании описанных данных приводятся сведения о возможных перспективах применения γδТ-клеток в терапии некоторых заболеваний.

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