mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-EFO-2944mimmun-2944Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESОсобенности экспрессии рецепторов CD16 и NKG2D NK-клетками, NKT-клетками и Т-лимфоцитами периферической крови, ассоциированные с бесплодием у женщинExpression features of CD16 and NKG2D receptors by NK cells, NKT cells and T lymphocytes of peripheral blood associated with female infertilityhttps://orcid.org/0000-0003-1328-8157МихайловаВ. А.MikhailovaV. A.

Михайлова Валентина Анатольевна – д.б.н., ведущий научный сотрудник лаборатории межклеточных взаимодействий, отдел иммунологии и межклеточных взаимодействий 

Санкт-Петербург

Mikhailova Valentina A., PhD, MD (Biology), Leading Researcher, Laboratory of Intercellular Interactions, Department of Immunology and Intercellular Interactions

St. Petersburg

mva_spb@mail.ruhttps://orcid.org/0000-0001-5313-2910ДавыдоваА. А.DavydovaA. A.

Давыдова Алина Алексеевна – младший научный сотрудник лаборатории межклеточных взаимодействий, отдел иммунологии и межклеточных взаимодействий 

Санкт-Петербург

Davydova Alina A., Junior Researcher, Laboratory of Intercellular Interactions, Department of Immunology and Intercellular Interactions

St. Petersburg

alyadavydova@gmail.comhttps://orcid.org/0000-0001-6971-7024ЗагайноваВ. А.ZagaynovaV. A.

Загайнова Валерия Алексеевна – врач – акушер-гинеколог отделения вспомогательных репродуктивных технологий 

Санкт-Петербург

Zagaynova Valeria A., Obstetrician-Gynecologist, Department of Assisted Reproductive Technologies

St. Petersburg

zagaynovav.al.52@mail.ruhttps://orcid.org/0000-0001-6078-1791МаркоО. Б.MarkoO. B.

Марко Оксана Богдановна – младший научный сотрудник лаборатории межклеточных взаимодействий, отдел иммунологии и межклеточных взаимодействий 

Санкт-Петербург

Marko Oksana B., Junior Researcher, Laboratory of Intercellular Interactions, Department of Immunology and Intercellular Interactions

St. Petersburg

okmarko@ya.ruhttps://orcid.org/0009-0009-0741-7101МкртчянЭ. Р.MkrtchyanE. R.

Мкртчян Эдгар Рафикович – лаборант лаборатории межклеточных взаимодействий, отдел иммунологии и межклеточных взаимодействий 

Санкт-Петербург

Mkrtchyan Edgar R., Laboratory Assistant, Laboratory of Intercellular Interactions, Department of Immunology and Intercellular Interactions

St. Petersburg

ed.mkk@mail.ruЖгулеваА. С.ZhgulevaA. S.

Жгулева Александра Станиславовна – лаборант лаборатории межклеточных взаимодействий, отдел иммунологии и межклеточных взаимодействий 

Санкт-Петербург

Zhguleva Aleksandra S., Laboratory Assistant, Laboratory of Intercellular Interactions, Department of Immunology and Intercellular Interactions

St. Petersburg

zhguleva@scamt-itmo.ruБакулинаО. А.BakulinaO. A.

Бакулина Ольга Андреевна – лаборант лаборатории межклеточных взаимодействий, отдел иммунологии и межклеточных взаимодействий 

Санкт-Петербург

Bakulina Olga A., Laboratory Assistant, Laboratory of Intercellular Interactions, Department of Immunology and Intercellular Interactions

St. Petersburg

olya.bakulina.03@mail.ruhttps://orcid.org/0000-0003-1560-7529СельковС. А.SelkovS. A.

Сельков Сергей Алексеевич – д.м.н., профессор, заслуженный деятель науки РФ, главный научный сотрудник отдела иммунологии и межклеточных взаимодействий 

Санкт-Петербург

Selkov Sergey A., PhD, MD (Medicine), Professor, Honored Scientist of the Russian Federation, Chief Researcher, Department of Immunology and Intercellular Interactions

St. Petersburg

selkovsa@mail.ruhttps://orcid.org/0000-0002-6542-5953БеспаловаО. Н.BespalovaO. N.

Беспалова Олеся Николаевна – д.м.н., заместитель директора по научной работе 

Санкт-Петербург

Bespalova Olesya N., PhD, MD (Medicine), Deputy Director for Research

St. Petersburg

shiggerra@mail.ruhttps://orcid.org/0000-0002-5749-2531СоколовД. И.SokolovD. I.

Соколов Дмитрий Игоревич – д.б.н., заведующий отделом иммунологии и межклеточных взаимодействий 

Санкт-Петербург

Sokolov Dmitry I., PhD, MD (Biology), Head, Department of Immunology and Intercellular Interactions

St. Petersburg

 

falcojugger@yandex.ruФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии имени Д.О. Отта»РоссияD. Ott Research Institute for Obstetrics, Gynecology and ReproductologyRussian Federation202507072025274789802Copyright © Михайлова В.А., Давыдова А.А., Загайнова В.А., Марко О.Б., Мкртчян Э.Р., Жгулева А.С., Бакулина О.А., Сельков С.А., Беспалова О.Н., Соколов Д.И., 20252025Михайлова В.А., Давыдова А.А., Загайнова В.А., Марко О.Б., Мкртчян Э.Р., Жгулева А.С., Бакулина О.А., Сельков С.А., Беспалова О.Н., Соколов Д.И.Mikhailova V.A., Davydova A.A., Zagaynova V.A., Marko O.B., Mkrtchyan E.R., Zhguleva A.S., Bakulina O.A., Selkov S.A., Bespalova O.N., 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/2944

Рост частоты встречаемости бесплодия определяет актуальность исследования вклада различных клеточных факторов, в том числе клеток иммунной системы, в патогенез этой патологии. В литературе описаны изменения активации NK-клеток в децидуальной оболочке и периферической крови при бесплодии, а также представительства NKT-клеток и Т-лимфоцитов в матке при невынашивании беременности (НБ). Для NK-клеток и NKT-клеток характерна экспрессия активационного рецептора NKG2D и рецептора к Fc-фрагменту иммуноглобулинов G – CD16. Отдельные популяции Т-лимфоцитов экспрессируют NKG2D. Целью работы явился анализ экспрессии рецепторов CD16 и NKG2D NK-клетками, NKT-клетками и рецептора NKG2D Т-лимфоцитами периферической крови у женщин с бесплодием. Обследовано 60 женщин с бесплодием. Группу контроля составили здоровые небеременные фертильные женщины (n = 17). Из периферической крови обследованных женщин получали мононуклеарные клетки, которые обрабатывали моноклональными антителами к CD45, CD14, CD3, CD56, CD16, NKG2D. Установлено, что у пациенток с первичным бесплодием интенсивность экспрессии рецептора NKG2D популяцией NKT-клеток периферической крови была ниже, чем у здоровых небеременных фертильных женщин. Установленное различие может быть обусловлено отсутствием в анамнезе имплантаций эмбриона у пациенток с первичным бесплодием и, соответственно, отсутствием влияния цитокинового и клеточного микроокружения, характерного для первого триместра беременности. У пациенток с вторичным бесплодием и НБ снижено относительное количество CD16+NK-клеток и CD16+NKG2D-NK-клеток периферической крови по сравнению с этим параметром у женщин с вторичным бесплодием без НБ в анамнезе. Относительное количество CD16+NK-клеток и CD16+NKG2D-NK-клеток периферической крови также было снижено у пациенток с вторичным бесплодием и НБ по сравнению с группой пациенток с первичным бесплодием и группой здоровых небеременных фертильных женщин. Установлено, что интенсивность экспрессии CD16 NK-клетками была снижена в подгруппе женщин с вторичным бесплодием и НБ в анамнезе по сравнению с группой контроля и подгруппой женщин с вторичным бесплодием без НБ в анамнезе. Различий к экспрессии NKG2D T-лимфоцитами при бесплодии не установлено. Сниженная экспрессия CD16 NK-клетками женщин с вторичным бесплодием и НБ может являться отражением нарушения функциональной дифференцировки NK-клеток при этой патологии.

The increasing incidence of infertility determines relevance of studying various cellular factors, including immune cells, in pathogenesis of this disorder. In cases of infertility, some changes are described in NK cell activation in decidual and peripheral blood cells, as well as in representation of NKT cells and T lymphocytes in uterus at miscarriage (MC). NK cells and NKT cells are characterized by expression of activating receptor NKG2D and a receptor for immunoglobulin G Fc-region CD16. Distinct populations of T lymphocytes express NKG2D. The aim of the present study was to analyze the expression of CD16 and NKG2D by NK cells, NKT cells and NKG2D receptor by peripheral blood T lymphocytes. We examined 60 women with infertility. The control group consisted of healthy non-pregnant fertile women (n = 17). Mononuclear cells were obtained from peripheral blood and treated with monoclonal antibodies to CD45, CD14, CD3, CD56, CD16, NKG2D. The intensity of NKG2D receptor expression on peripheral blood NKT cells in patients with primary infertility proved to be lower than in healthy non-pregnant fertile women. This difference may be caused by the absence of an embryo implantation in previous history of primary infertility and, accordingly, lacking influence of cytokines and cellular microenvironment specific for first trimester of pregnancy. In patients with secondary infertility and miscarriage (MC), the relative numbers of CD16+NK cells and CD16+NKG2D-NK cells in peripheral blood were reduced when compared to the women with secondary infertility without history of MC. Relative numbers of CD16+NK cells and CD16+NKG2D-NK cells in peripheral blood were also reduced in patients with secondary infertility and MC compared to patients with primary infertility and to healthy non-pregnant fertile women. CD16 expression intensity of NK cells was shown to be reduced in subgroup of women with secondary infertility and a history of MC compared to control group and to women with secondary infertility without a history of MC. No differences in NKG2D expression by T lymphocytes associated with infertility were found. Reduced CD16 expression by NK cells of women with secondary infertility and MC may reflect the impaired functional differentiation of NK cells associated with this condition.

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