mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-2018-5-621-638mimmun-1631Research ArticleОБЗОРЫREVIEWSРОЛЬ РАЗЛИЧНЫХ СУБПОПУЛЯЦИЙ CD8+Т-ЛИМФОЦИТОВ ПРИ БЕРЕМЕННОСТИTHE ROLE OF SUBPOPULATIONS OF CD8+ T LYMPHOCYTES IN THE DEVELOPMENT OF PREGNANCYСтепановаО. И.StepanovaO. I.

к.б.н., старший научный сотрудник лаборатории межклеточных взаимодействий, отдел иммунологии и межклеточных взаимодействий.

PhD (Biology), Senior Research Associate, Cell Interactions Laboratory, Department of Immunology and Cell Interactions.

БаженовД. О.BazhenovD. O.

младший научный сотрудник лаборатории межклеточных взаимодействий, отдел иммунологии и межклеточных взаимодействий.

Junior Research Associate, Cell Interactions Laboratory, Department of Immunology and Cell Interactions.

ХохловаE. В.KhokhlovaE. V.

лаборант-исследователь лаборатории межклеточных взаимодействий, отдел иммунологии и межклеточных взаимодействий.

E.V., Research Assistant, Cell Interactions Laboratory, Department of Immunology and Cell Interactions/

КоганИ. Ю.KoganI. Yu.

д.м.н., член-корр. РАН, профессор, врио директора.

PhD, MD (Medicine), Corresponding Member, Russian Academy of Sciences, Professor, Acting Director/

СоколовД. И.SokolovD. I.

д.б.н., заведующий лабораторией межклеточных взаимодействий, отдел иммунологии и межклеточных взаимодействий. 

199034, Россия, Санкт-Петербург, Менделеевская линия, 3.

PhD, MD (Biology), Head, Cell Interactions Laboratory, Department of Immunology and Cell Interactions.

199034, Russian Federation, St. Petersburg, Mendeleevskaya line, 3.

falcojuggen@yandex.ruСельковС. А.SelkovS. A.

д.м.н., профессор, руководитель отдела иммунологии и межклеточных взаимодействий.

PhD, MD (Medicine), Professor, Head, Department of Immunology and Cell Interactions.

ФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии имени Д.О. Отта».РоссияD. Ott Research Institute of Obstetrics, Ginecology and Reproductology.Russian FederationФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии имени Д.О. Отта»; ГБОУ ВПО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения РФ.РоссияD. Ott Research Institute of Obstetrics, Ginecology and Reproductology; First St. Petersburg State I. Pavlov Medical University.Russian Federation201804112018205621638Copyright © Степанова О.И., Баженов Д.О., Хохлова E.В., Коган И.Ю., Соколов Д.И., Сельков С.А., 20182018Степанова О.И., Баженов Д.О., Хохлова E.В., Коган И.Ю., Соколов Д.И., Сельков С.А.Stepanova O.I., Bazhenov D.O., Khokhlova E.V., Kogan I.Y., Sokolov D.I., Selkov S.A.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/1631

В настоящее время выявлено существование широкого спектра субпопуляций CD8+Тлимфоцитов, среди которых выделяют субпопуляции наивных клеток, клеток памяти, регуляторных. Кроме клеток с высоким уровнем цитотоксической активности, выявлены субпопуляции, обладающие выраженной регуляторной активностью. Каждая субпопуляция характеризуется совокупностью продуцируемых медиаторов, поверхностных и внутриклеточных маркеров, позволяющих предположить их различную функциональную активность в условиях in vivo. В настоящем обзоре описана классификация CD8+Т-лимфоцитов, учитывающая их морфофункциональные признаки. Традиционно считается, что CD8+Т-лимфоциты являются популяцией лимфоцитов, обладающей высокой цитотоксической активностью, что имеет чрезвычайное значение в условиях инвазии полуалогенных плодовых клеток в эндометрий при беременности. Доля CD8+Т-лимфоцитов в децидуальной оболочке довольно велика. В обзоре обсуждаются известные на сегодняшний день механизмы регуляции дифференцировки, избирательной миграции и функциональной активности CD8+Т-лимфоцитов в децидуальной оболочке и плаценте при беременности. Основными факторами цитотоксического действия CD8+Т-лимфоцитов являются перфорин и гранзим. К регуляторным медиаторам CD8+Тлимфоцитов относят цитокины IL-2, IL-5, IL-13, IFNγ, IL-17, TGF-β и IL-10. Для развития эффекторных свойств CD8+Т-лимфоцитов необходима антигенная стимуляция, которую обеспечивает взаимодействие CD8+Т-лимфоцитов с активированными CD4+Т-лимфоцитами или дендритными клетками, воздействие цитокинов. Условия специфической дифференцировки CD8+Т-лимфоцитов формируются за счет различного характера микроокружения. В децидуальной оболочке при беременности наблюдается концентрация CD8+Т-лимфоцитов, но их фенотип и функциональная активность отличаются от CD8+Т-лимфоцитов периферической крови. В настоящее время продолжается изучение механизмов избирательной миграции CD8+Т-лимфоцитов с регуляторными свойствами в децидуальную оболочку. Полагают, что это обеспечивается при участии хемокиновых рецепторов CXCR3 и CCR5, цитокинов IL-6 и IL-15. Характер активности CD8+Т-лимфоцитов и продукция ими цитокинов CSF2, IFNγ, IL-1β, IL-2, IL-6, IL-8,IL-10, IL-12 и TNFα в децидуальной оболочке имеют решающее значение для успешной инвазии клеток трофобласта. В свою очередь, клетки трофобла ста и плаценты способствуют формированию пула регуляторных CD8+Т-лимфоцитов в децидуальной оболочке, способны индуцировать апоптоз CD8+Т-лимфоцитов. Таким образом, взаимодействие CD8+Т-лимфоцитов матери и трофобласта в зоне маточно-плацентарного контакта является важным звеном в формировании иммунологической толлерантности в системе мать-плод.

At the present time, a broad spectrum of CD8+ T lymphocyte subsets is revealed, including naïve cells, memory cells and regulatory subpopulations. Along with cells with high cytolytic activity, some subsets with marked regulatory activity were found there. Each subpopulation is characterized by a set of produced mediators, surface and intracellular markers allowing to suggest their differential in vivo functional activity. The present review article proposes a classification of CD8+ Т cells which takes into account their morphological and functional features. According to conventional view, the CD8+ Т lymphocytes is a cell population exhibiting high cytotoxic ability which is of critical significance in pregnancy, under the conditions of semi-allogenic fetal cell invasion into the endometrium. The fraction of CD8+ T cells is rather high in decidual structures. The review discusses the known mechanisms of differentiation regulation, selective migration and activity of CD8+ T cells in decidual membrane and placenta in the course of pregnancy. Perforine and granzyme are the main cytotoxicity factors of CD8+ Т cells. IL-2, IL-5, IL-13, IFNγ, IL-17, TGF-β and IL-10 cytokines are considered regulatory mediators of CD8+ cells. To induce the effector properties of CD8+ T cells, an antigenic stimulation is required, which is provided by interactions between the CD8+ Т cells and activated CD4+ Т cells or dendritic cells, cytokine effects. Specific differentiation of the CD8+ T cells is determined by differences in microenvironvent. In the course of pregnancy, accumulation of CD8+ Т cells is observed in decidual membrane, but their phenotype and functional properties differ from CD8+ Т cells in peripheral blood. At present time, the mechanisms of selective CD8+ T cell migration to decidual membrane are studied. These events are suggested to be mediated by means of CXCR3 and CCR5 chemokine receptors, IL-6 and IL-15 cytokines. The features of CD8+ Т cell activities, and production of some cytokines, e.g., CSF2, IFNγ, IL-1β, IL-2, IL-6, IL-8,IL-10, IL-12 and TNFα in decidual membrane and is of critical significance for effective invasion of trophoblast cells. In turn, the trophoblast and placental cells promote development of regulatory CD8+ Т lymphocytes in decidual membrane, being able to induce CD8+ T cell apoptosis in decidual membrane. Hence, interaction between the maternal CD8+ T cells and trophoblast in the area of uterine-placental contact is an important link during development of immunological tolerance in the maternal/fetal system.

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