mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-NKC-2330mimmun-2330Research ArticleОБЗОРЫREVIEWSЕстественные киллеры: происхождение, фенотип, функции.Natural killer cells: origin, phenotype, functionТыщукЕ. В.TyshchukE. V.

Тыщук Елизавета Владимировна – лаборант-исследователь лаборатории межклеточных взаимодействий, отдел иммунологии и межклеточных взаимодействий.

199034, Санкт-Петербург, Менделеевская линия, 3. Тел.: 8 (931) 963-85-78

Tyshchuk Elizaveta V. - Research Assistant, Laboratory of Intercellular Interactions, Department of Immunology and Intercellular Interactions, D. Ott RIOGR.

199034, St. Petersburg, Mendeleevskaya line, 3. Phone: 7 (931) 963-85-78.

tyshhuk.elizaveta@gmail.comМихайловаВ. А.MikhailovaV. A.

Кандидат биологических наук, старший научный сотрудник лаборатории межклеточных взаимодействий, отдел иммунологии и межклеточных взаимодействий НИИАГР имени Д.О. Отта; кафедра иммунологии Первый С-ПбГМУ имени академика И.П. Павлова.

Санкт-Петербург

PhD (Biology), Senior Research Associate, Laboratory of Intercellular Interactions, Department of Immunology and Intercellular Interactions, D. Ott RIOGR; Department of Immunology, First St. Petersburg State I. Pavlov MU.

St. Petersburg

СельковС. А.SelkovS. A.

Доктор медицинских наук, профессор, заслуженный деятель науки РФ, заведующий отделом иммунологии и межклеточных взаимодействий НИИАГР имени Д.О. Отта; профессор кафедры иммунологии Первый С-ПбГМУ имени академика И.П. Павлова.

Санкт-Петербург

PhD, MD (Medicine), Professor, Honored Science Worker, Head, Department of Immunology and Intercellular Interactions, D. Ott RIOGR; Professor, Department of Immunology, First St. Petersburg State I. Pavlov MU.

St. Petersburg

СоколовД. И.SokolovD. I.

Доктор биологических наук, заведующий лабораторией межклеточных взаимодействий, отдел иммунологии и межклеточных взаимодействий НИИАГР имени Д.О. Отта; кафедра иммунологии Первый С-ПбГМУ имени академика И.П. Павлова.

Санкт-Петербург

PhD, MD (Biology), Head, Laboratory of Intercellular Interactions, Department of Immunology and Intercellular Interactions, D. Ott Research Institute of Obstetrics, Gynecology and Reproductology; Department of Immunology, First St. Petersburg State I. Pavlov MU.

St. Petersburg

ФГБНУ Научно-исследовательский институт акушерства, гинекологии и репродуктологии имени Д.О. ОттаРоссияD. Ott Research Institute of Obstetrics, Gynecology and Reproductology, St. Petersburg, Russian FederationRussian FederationФГБНУ Научно-исследовательский институт акушерства, гинекологии и репродуктологии имени Д.О. Отта; ФГБОУ ВО Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова Министерства здравоохранения РФРоссияD. Ott Research Institute of Obstetrics, Gynecology and Reproductology, St. Petersburg, Russian FederationRussian Federation20212012202123612071228Copyright © Тыщук Е.В., Михайлова В.А., Сельков С.А., Соколов Д.И., 20212021Тыщук Е.В., Михайлова В.А., Сельков С.А., Соколов Д.И.Tyshchuk E.V., Mikhailova V.A., Selkov S.A., Sokolov D.I.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/2330

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.

 

Natural killer cells (NK) are innate immune lymphocytes produced in the bone marrow. Isolation of NK cells as a separate population of lymphocytes is related to discovery of their ability to induce the death of tumor cells without prior sensitization. In this review, an attempt was made to systematize the numerous data on the biology of NK cells presented in the literature. The authors consider the stages of NK cells` differentiation from a common lymphoid progenitor (CLP) in the bone marrow, describe two functionally different populations of mature NK cells – CD56brightCDl6- and CD56dimCD16+. In addition, the role of cytokines and chemokines in the development of NK cells is discussed. The review includes data on the spectrum of molecules expressed by NK cells: adhesion molecules (LFA-1, LFA-2, LFA-3; αMβ2, αXβ2, L-selectin, VLA-4, VLA-5; PECAM-1; CEACAM-1), cytokine receptors (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), as well as receptors that regulate the activity of NK cells (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). The authors also examine the mechanisms of implementing cytotoxic activity by NK cells, including cytotoxicity, via expression of MHC-I-specific receptors, CD16 Fc receptors, receptors and ligands of apoptosis (Fas-FasL and TRAIL-TRAILR) as well as other receptors. The review describes in detail the structure of immunological synapse between the NK cell and target cell, receptor interactions, and the role of the cytoskeleton in its formation. The data are summarized on the variants of exocytosis of lytic granules by NK cells, including complete or partial fusion of vesicles with the plasma membrane, exocytosis of vesicles containing perforin and FasL, and the formation of microvesicles containing granzyme B. The review also describes data on ability of NK cells to maintain activated state for a long time, as well as to maintain contact with several targets at the same time. In addition to the functions inherent in natural killers as cells of innate immunity, the authors point out their ability to exhibit the features of cells of adaptive immunity. In general, a variety of mechanisms that regulate the activity of NK cells may complement the specific functions of lymphocytes, thus making the immune system more efficient.

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