Russian Journal of PhysiologyRussian Journal of PhysiologyРоссийский физиологический журнал им. И.М. Сеченова0869-81392658-655XThe Russian Academy of Sciences65156410.31857/S0869813923050072XRCAREEXPERIMENTAL ARTICLESЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИTim-3, CD9 Molecule Expressions on Natural Killer (NK) and T-Lymphocytes with NK Functions (NKT) of the Peripheral Blood at Different Trimesters of Physiological PregnancyЭкспрессия молекул Tim-3 и CD9 на натуральных киллерах (NK) и Т-лимфоцитах с функциями NK (NKT) периферической крови в разные сроки физиологической беременностиOrlovaE. G.ОрловаЕ. Г.orlova_katy@mail.ruLoginovaО. А.ЛогиноваО. А.orlova_katy@mail.ruGorbunovaО. L.ГорбуноваО. Л.orlova_katy@mail.ruKarimovaN. V.КаримоваН. В.orlova_katy@mail.ruShirshevS. V.ШиршевС. В.orlova_katy@mail.ruInstitute of Ecology and Genetics of Microorganisms RAS – Branch of Perm Federal Research Center UB RASИнститут экологии и генетики микроорганизмов УрО РАНLLC Centralized Clinical and Diagnostic LaboratoryООО Централизованная клинико-диагностическая лаборатория01052023109557258701022025Copyright ©; 2023, Е.Г. Орлова, О.А. Логинова, О.Л. Горбунова, Н.В. Каримова, С.В. ШиршевCopyright ©; 2023, Е.Г. Орлова, О.А. Логинова, О.Л. Горбунова, Н.В. Каримова, С.В. Ширшев2023Е.Г. Орлова, О.А. Логинова, О.Л. Горбунова, Н.В. Каримова, С.В. ШиршевЕ.Г. Орлова, О.А. Логинова, О.Л. Горбунова, Н.В. Каримова, С.В. Ширшевhttps://journals.eco-vector.com/0869-8139/article/view/651564

Natural killer cells (NK) and T-lymphocytes with NK functions (NKT) are the leading effectors of the mother’s immune tolerance to a semi-allogeneic fetus and have a fetal trophic effect during physiological pregnancy. Tim-3 (T-cell Ig and mucin domain-containing protein 3) and CD9 molecules play a critical role in the immunoregulatory and fetal trophic functions of NK and NKT, but their expression in peripheral blood cells has not been studied. The aim of this work was to study the expression of Tim-3 and CD9 in peripheral blood NK and NKT during physiological pregnancy. The object of the study was the peripheral blood of healthy women in I and III trimesters of a physiological pregnancy. The control group consisted of healthy non-pregnant women in the first phase of the menstrual cycle. Expression of Tim-3, CD9 molecules was analyzed by flow cytometry on regulatory NK (CD16–CD56bright) and NKT (CD16–CD56+), cytotoxic NK (CD16+CD56dim/–) and NKT (CD16+CD56+). It was found that in the first trimester of pregnancy, the total number and subpopulation composition of NK and NKT cells did not change. Tim-3 expression increased in all NK and NKT subpopulations, except for cytotoxic CD16+CD56dimNK. CD9 expression increased in all NK subpopulations, but in NKT did not differ from non-pregnant. At the same time, a direct correlation between CD9 and Tim-3 expressions was revealed in regulatory NK and NKT in the first trimester of pregnancy. In the third trimester, the regulatory CD16–CD56brightNK number increased, while cytotoxic CD16+CD56dimNK and regulatory CD16–CD56+NKT decreased compared to non-pregnant women. The number of CD16+CD56–NK did not change in I and III trimesters of a physiological pregnancy. Tim-3 expression was upregulated in all NK and cytotoxic NKT subpopulations, while CD9 was upregulated only in regulatory NKs. Thus, Tim-3 and CD9 molecule expressions of s on different NK and NKT subpopulations changed during I and III trimesters of a physiological pregnancy, which plays an important role in the regulation of their phenotype and functions.

При физиологически протекающей беременности натуральные киллеры (NK) и Т-лимфоциты с функциями NK (NKT) являются ведущими эффекторами иммунной толерантности организма матери к полуаллогенному плоду, а также выполняют фетотрофическую функцию. Молекулы Tim-3 (T-cell Ig and mucin domain-containing protein 3) и CD9 играют критическую роль в реализации иммунорегуляторной и фетотрофической функций NK и NKT, однако их экспрессия на клетках периферической крови не изучена. Цель работы – исследовать экспрессию Tim-3, CD9 на субпопуляциях NK и NKT периферической крови в разные сроки физиологически протекающей беременности. Объектом исследования являлась периферическая кровь условно-здоровых женщин в I и III триместрах физиологически протекающей беременности. Группу сравнения составили условно-здоровые небеременные женщины в I фазе менструального цикла. Экспрессию молекул Tim-3, CD9 анализировали методом проточной цитофлюориметрии на регуляторных NK (CD16–CD56bright) и NKT (CD16–CD56+), цитотоксических NK (CD16+CD56dim/–) и NKT (CD16+CD56+). Установлено, что в I триместре беременности количество и соотношение регуляторных и цитотоксических NK и NKT не менялось. Экспрессия Tim-3 увеличивалась на всех субпопуляциях NK и NKT за исключением цитотоксических CD16+CD56dimNK. Экспрессия CD9 возрастала на всех субпопуляциях NK, а на NKT не отличалась от небеременных. При этом на регуляторных NK и NKT в I триместре беременности выявлена прямая корреляция экспрессии CD9 и Tim-3. В III триместре количество регуляторных CD16–CD56brightNK увеличивалось, а цитотоксических CD16+CD56dimNK и регуляторных CD16–CD56+NKТ снижалось по сравнению с небеременными. Количество CD16+CD56–NK не менялось по триместрам беременности. Экспрессия Tim-3 усиливалась на всех субпопуляциях NK и цитотоксических NKТ, а CD9 повышалась только на регуляторных NK. Таким образом, экспрессия молекул Tim-3 и CD9 на разных субпопуляциях NK и NKT менялась по триместрам, что играет важную роль в регуляции их фенотипа и функций при беременности.

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