astmedАстраханский медицинский журналAstrakhan medical journal1992-6499ФГБОУ ВО Астраханский ГМУ Минздрава России10.17021/1992-6499-2026-2-35-47astmed-730Research ArticleНАУЧНЫЕ ОБЗОРЫSCIENTIFIC REVIEWSСубпопуляции Т-хелперов и их биологические эффекты (обзор литературы)T-helper subpopulations and their biological effectshttps://orcid.org/0009-0004-5659-7464МоскалёвА. В.MoskalevA. V.

Москалев Александр Витальевич - доктор медицинских наук, профессор, профессор кафедры микробиологии.

Санкт-Петербург

Alexander V. Moskalev - Dr. Sci. (Med.), Professor, Professor of the Department, S.M. Kirov Military Medical Academy.

Saint Petersburg

alexmav195223@yandex.ruhttps://orcid.org/0000-0001-8755-2219ГумилевскийБ. Ю.GumilevskiyB. Yu.

Гумилевский Борис Юрьевич - доктор медицинских наук, профессор, заведующий кафедрой микробиологии.

Санкт-Петербург

Boris Yu. Gumilevskiy - Dr. Sci. (Med.), Professor, Head of the Department, S.M. Kirov Military Medical Academy.

Saint Petersburg

gumbu@mail.ruhttps://orcid.org/0000-0001-9852-9372ГумилевскаяО. П.GumilevskayaO. P.

Гумилевская Оксана Петровна - доктор медицинских наук, доцент, профессор кафедры патологической физиологии.

Санкт-Петербург

Oksana P. Gumilevskaya - Dr. Sci. (Med.), Associate Professor, Professor of the Department, S.M. Kirov Military Medical Academy.

Saint Petersburg

gumbu@mail.ruhttps://orcid.org/0000-0002-3960-830XЖестковА. В.ZhestkovA. V.

Жестков Александр Викторович - доктор медицинских наук, профессор, заведующий кафедрой клинической медицины.

Самара

Alexander V. Zhestkov - Dr. Sci. (Med.), Professor, Head of the Department, Medical University Reaviz.

Samara

avzhestkov2015@yandex.ruhttps://orcid.org/0000-0003-4168-4851БашкинаО. А.BashkinaO. A.

Башкина Ольга Александровна - доктор медицинских наук, профессор, заведующий кафедрой факультетской педиатрии.

Астрахань

Olga A. Bashkina - Dr. Sci. (Med.), Professor, Head of the Department, Astrakhan State Medical University.

Astrakhan

bashkina1@mail.ruhttps://orcid.org/0009-0000-0552-2762ВласоваЛ. Д.VlasovaL. D.

Власова Любовь Денисовна - студент, Институт профилактической медицины.

Самара

Lyubov D. Vlasova - student, Institute of Preventive Medicine, Samara State Medical University.

Samara

ldv555555@gmail.comhttps://orcid.org/0009-0008-1695-9423СтароваЮ. А.StarovaYu. A.

Старова Юлия Александровна - ассистент кафедры клинической медицины.

Самара

Yuliya A. Starova - Assistant of the Department, Medical University Reaviz.

Samara

doc.starova@yandex.ruВоенно-медицинская академия им. С.М. КироваРоссияKirov Military Medical AcademyRussian FederationМедицинский университет «Реавиз»РоссияMedical University ReavizRussian FederationАстраханский государственный медицинский университетРоссияAstrakhan State Medical UniversityRussian FederationСамарский государственный медицинский университетРоссияSamara State Medical UniversityRussian Federation2026040820262123547Copyright © Москалёв А.В., Гумилевский Б.Ю., Гумилевская О.П., Жестков А.В., Башкина О.А., Власова Л.Д., Старова Ю.А., 20262026Москалёв А.В., Гумилевский Б.Ю., Гумилевская О.П., Жестков А.В., Башкина О.А., Власова Л.Д., Старова Ю.А.Moskalev A.V., Gumilevskiy B.Y., Gumilevskaya O.P., Zhestkov A.V., Bashkina O.A., Vlasova L.D., Starova Y.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.astmedj.ru/jour/article/view/730

Рассмотрены биологические особенности субпопуляции Т-хелперов: Th1, Th2, Th17, Th9, Th22, фолликулярных Т-лимфоцитов. Охарактеризованы соответствующие транскрипционные факторы, сигнальные пути, участвующие в биологических эффектах CD4+Т-лимфоцитов и секретируемые ими интерлейкины, влияющие на развитие иммунного ответа. Эффективность созревания, дифференцировка Т-хелперов зависят от адгезионных молекул и гуморальных факторов. Th1-типа критически важны в развитии первичных иммунодефицитных состояний, гомозиготных мутаций, с которыми связаны рецепторы IFN-γ, IL-12 и сигнальные белки STAT1. В биологической активации Th2-типа участвуют IL-25, IL-33 и стромальный лимфопоэтин тимуса. В созревании и дифференцировке Т-лимфоцитов принимают участие JAK-3, STAT1-6, T_T-BET, GATA-3. Отклонения в функционировании перечисленных молекул приводят к изменениям биологических эффектов Th1-типа и Th2-типа. Таким образом, биологические эффекты субпопуляции Т-хелперов имеют большое значение в реализации реакций врожденного и приобретенного иммунитета, безусловно актуальными представляются новые исследования в этой области.

The biological features of a subpopulation of T helper cells: Th1, Th2, Th17, Th9, Th22, follicular T lymphocytes are considered. The corresponding transcription factors, signaling pathways involved in the biological effects of CD4+T lymphocytes, and interleukins secreted by them, which influence the development of the immune response, are characterized. The maturation efficiency and differentiation of T-helper cells depend on adhesion molecules and humoral factors. Thl-type are critically important in the development of primary immunodeficiency states, homozygous mutations associated with IFN-γ, IL-12 receptors, and STAT1 signaling proteins. IL-25, IL-33, and thymus stromal lymphopoietin are involved in the biological activation of Th2-type. JAK-3, STAT1-6, T_T-BET, and GATA-3 are involved in the maturation and differentiation of T-lymphocytes. Deviations in the functioning of these molecules lead to changes in the biological effects of Th1-type and Th2-type. Thus, the biological effects of the T-helper subpopulation are of great importance in the implementation of innate and acquired immune responses, and new research in this area is certainly relevant.

геныинтерлейкинырецепторыхемокинытранскрипционные факторыТ-лимфоцитыgenesinterleukinsreceptorschemokinestranscription factorsT-lymphocytesReferencesМоскалев А. В., Гумилевский Б. Ю., Апчел А. В., Цыган В. Н. Т-лимфоциты – «цензорные» клетки иммунной системы // Вестник Российской военно-медицинской академии. 2019. № 2 (66). С. 191–197. doi: 10.17816/brmma25943.Moskalev A. V., Gumilevskii B. Yu., Apchel A. V., Tsygan V. N. T-lymphocytes – “censor” cells of the immune system. Vestnik Rossiiskoy voenno-meditsinskoy akademii = Bulletin of the Russian Military Medical Academy. 2019; 2 (66): 191–197. doi: 10.17816/brmma25943 (In Russ.).Москалев А. В., Гумилевский Б. Ю., Апчел В. Я., Цыган В. Н. Клеточные и гуморальные факторы врожденного противовирусного иммунитета // Вестник Российской военно-медицинской академии. 2022. Т. 24, вып. 4. С. 751–764. doi: 10.17816/brmma108136.Moskalev A. V., Gumilevskii B. Yu., Apchel V. Ya., Tsygan V. N. Cellular and humoral factors of innate antiviral immunity. Vestnik Rossiiskoy voenno-meditsinskoy akademii = Bulletin of the Russian Military Medical Academy. 2022; 24 (4): 751–764. doi: 10.17816/brmma108136 (In Russ.).Москалев А. В., Гумилевский Б. Ю., Апчел В. Я., Цыган В. Н. Особенности развития адаптивного противовирусного иммунного ответа // Вестник Российской военно-медицинской академии. 2022. Т. 24, вып. 4. С. 789–800. doi: 10.17816/brmma109497.Moskalev A. V., Gumilevskii B. Yu., Apchel V. Ya., Tsygan V. N. Features of the development of adaptive antiviral immune response. Vestnik Rossiiskoy voenno-meditsinskoy akademii = Bulletin of the Russian Military Medical Academy. 2022; 24 (4): 789–800. doi: 10.17816/brmma109497 (In Russ.).Baumjohann D., Ansel K. M. MicroRNA-mediated regulation of T helper cell differentiation and plasticity // Nature Reviews Immunology. 2013. Vol. 13. P. 666–678. doi: 10.1038/nri3494.Baumjohann D., Ansel K. M. MicroRNA-mediated regulation of T helper cell differentiation and plasticity. Nature Reviews Immunology. 2013; 13: 666–678. doi: 10.1038/nri3494.Murphy K. M., Stockinger B. Effector T cell plasticity: flexibility in the face of changing circumstances // Nature Immunology. 2010. Vol. 11. P. 674–680. doi: 10.1038/ni.1899.Murphy K. M., Stockinger B. Effector T cell plasticity: flexibility in the face of changing circumstances. Nature Immunology. 2010; 11: 674–680. doi: 10.1038/ni.1899.Mackaness G. B. Cellular resistance to infection // Journal of Experimental Medicine. 1962. Vol. 116. P. 381–406. doi: 10.1084/jem.116.3.381.Mackaness G. B. Cellular resistance to infection. Journal of Experimental Medicine. 1962; 116: 381–406. doi: 10.1084/jem.116.3.381.Mosmann T. R., Cherwinski H., Bond M. W. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins // Journal of Immunology. 1986. Vol. 136. P. 2348–2357. doi: 10.4049/jimmunol.136.7.2348.Mosmann T. R., Cherwinski H., Bond M. W. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. Journal of Immunology. 1986; 136: 2348–2357. doi: 10.1016/j.immuni.2019.03.021.Nakayama T., Hirahara K., Onodera A. Th2 cells in health and disease // Annual Review of Immunology. 2017. Vol. 35. P. 53–84. doi: 10.1146/annurev-immunol-051116-052350.Nakayama T., Hirahara K., Onodera A. Th2 cells in health and disease. Annual Review of Immunology. 2017; 35: 53–84. doi: 10.1146/annurev-immunol-051116-052350.Pritchard G. H., Kedl R. M., Hunter C. A. The evolving role of T-bet in resistance to infection // Nature Reviews Immunology. 2019. Vol. 19. P. 398–410. doi: 10.1038/s41577-019-0157-9.Pritchard G. H., Kedl R. M., Hunter C. A. The evolving role of T-bet in resistance to infection. Nature Reviews Immunology. 2019; 19: 398–410. doi: 10.1016/j.immuni.2015.12.003.Kanno Y., Vahedi G., Hirahara K. Transcriptional and epigenetic control of T helper cell specification: molecular mechanisms underlying commitment and plasticity // Annual Review of Immunology. 2012. Vol. 30. P. 707–731. doi: 10.1146/annurev-immunol-020711-075058.Kanno Y., Vahedi G., Hirahara K. Transcriptional and epigenetic control of T helper cell specification: molecular mechanisms underlying commitment and plasticity. Annual Review of Immunology. 2012; 30: 707–731. doi: 10.1146/annurev-immunol-020711-075058.Mazzoni A., Maggi L., Liotta F. Biological and clinical significance of T helper 17 cell plasticity // Immunology. 2019. Vol. 158. P. 287–295. doi: 10.1111/imm.13124.Mazzoni A., Maggi L., Liotta F. Biological and clinical significance of T helper 17 cell plasticity. Immunology. 2019; 158: 287–295. doi: 10.1111/imm.13124.Patel D. D., Kuchroo V. K. Th17 cell pathway in human immunity: lessons from genetics and therapeutic interventions // Immunity. 2015. Vol. 43. P. 1040–1051. doi: 10.1016/j.immuni.2015.12.003.Patel D. D., Kuchroo V. K. Th17 cell pathway in human immunity: lessons from genetics and therapeutic interventions. Immunity. 2015; 43: 1040–1051. doi: 10.1016/j.immuni.2015.12.003.Pulendran B., Artis D. New paradigms in type 2 immunity // Science. 2012. Vol. 337. P. 431–435. doi: 10.1126/science.1221064.Pulendran B., Artis D. New paradigms in type 2 immunity. Science. 2012; 337: 431–435. doi: 10.1126/science.1221064.Ivashkiv L. B. IFNγ: signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy // Nature Reviews Immunology. 2018. Vol. 18. P. 545–558. doi: 10.1038/s41577-018-0029-z.Ivashkiv L. B. IFNγ: signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy. Nature Reviews Immunology. 2018; 18: 545–558. doi: 10.1038/s41577-018-0029-z.Sallusto F. Heterogeneity of human CD4(+) T cells against microbes // Annual Review of Immunology. 2016. Vol. 34. P. 317–334. doi: 10.1146/annurev-immunol-041015-055438.Sallusto F. Heterogeneity of human CD4(+) T cells against microbes. Annual Review of Immunology. 2016; 34: 317–334. doi: 10.1146/annurev-immunol-051116-052350.Schmitt N., Ueno H. Regulation of human helper T cell subset differentiation by cytokines // Current Opinion in Immunology. 2015. Vol. 34. P. 130–136. doi: 10.1016/j.coi.2015.03.007.Schmitt N., Ueno H. Regulation of human helper T cell subset differentiation by cytokines. Current Opinion in Immunology. 2015; 34: 130–136. doi: 10.1016/j.coi.2015.03.007.Sungnak W., Wang C., Kuchroo V. K. Multilayer regulation of CD4 T cell subset differentiation in the era of single cell genomics // Advances in Immunology. 2019. Vol. 141. P. 1–31. doi: 10.1016/bs.ai.2018.12.001.Sungnak W., Wang C., Kuchroo V. K. Multilayer regulation of CD4 T cell subset differentiation in the era of single cell genomics. Advances in Immunology. 2019; 141: 1–31. doi: 10.1016/bs.ai.2018.12.001.Tubo N. J., Jenkins M. K. TCR signal quantity and quality in CD4+ T cell differentiation // Trends in Immunology. 2014. Vol. 35. P. 591–596. doi: 10.1016/j.it.2014.09.008.Tubo N. J., Jenkins M. K. TCR signal quantity and quality in CD4+ T cell differentiation. Trends in Immunology. 2014; 35: 591–596. doi: 10.1016/j.it.2014.09.008.Vantourout P., Hayday A. Six-of-the-best: unique contributions of γδ T cells to immunology // Nature Reviews Immunology. 2013. Vol. 13. P. 88–100. doi: 10.1038/nri3384.Vantourout P., Hayday A. Six-of-the-best: unique contributions of γδ T cells to immunology. Nature Reviews Immunology. 2013; 13: 88–100. doi: 10.1038/nri3384.Walker J. A., McKenzie A. N. J. TH2 cell development and function // Nature Reviews Immunology. 2018. Vol. 18. P. 121–133. doi: 10.1038/nri.2017.118.Walker J. A., McKenzie A. N. J. TH2 cell development and function. Nature Reviews Immunology. 2018; 18: 121–133. doi: 10.1038/nri.2017.118.Wynn T. A. Type 2 cytokines: mechanisms and therapeutic strategies // Nature Reviews Immunology. 2015. Vol. 15. P. 271–282. doi: 10.1038/nri3831.Wynn T. A. Type 2 cytokines: mechanisms and therapeutic strategies. Nature Reviews Immunology. 2015; 15: 271–282. doi: 10.1038/nri3831.Wynn T. A., Chawla A., Pollard J. W. Macrophage biology in development, homeostasis and disease // Nature. 2013. Vol. 496. P. 445–455. doi: 10.1038/nature12034.Wynn T. A., Chawla A., Pollard J. W. Macrophage biology in development, homeostasis and disease. Nature. 2013; 496: 445–455. doi: 10.1038/nature12034.Sica A., Mantovani A. Macrophage plasticity and polarization: in vivo veritas // Journal of Clinical Investigation. 2012. Vol. 122. P. 787–795. doi: 10.1172/JCI59649.Sica A., Mantovani A. Macrophage plasticity and polarization: in vivo veritas. Journal of Clinical Investigation. 2012; 122: 787–795. doi: 10.1172/JCI59649.Szabo S. J., Kim S. T., Costa G. L. A novel transcription factor, T-bet, directs Th1 lineage commitment // Cell. 2000. Vol. 100. P. 655–669. doi: 10.1016/S0092-8674(00)80702-3.Szabo S. J., Kim S. T., Costa G. L. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell. 2000; 100: 655–669. doi: 10.1016/S0092-8674(00)80702-3.Zheng W., Flavell R. A. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells // Cell. 1997. Vol. 89. P. 587–596. doi: 10.1016/S0092-8674(00)80240-8.Zheng W., Flavell R. A. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell. 1997; 89: 587–596. doi: 10.1016/S0092-8674(00)80240-8.Schorer M., Kuchroo V. K., Joller N. Role of co-stimulatory molecules in T helper cell differentiation // Advances in Experimental Medicine and Biology. 2019. Vol. 1189. P. 153–177. doi: 10.1007/978-3-030-30583-9_8.Schorer M., Kuchroo V. K., Joller N. Role of co-stimulatory molecules in T helper cell differentiation. Advances in Experimental Medicine and Biology. 2019; 1189: 153–177. doi: 10.1007/978-3-030-30583-9_8.Van Dyken S. J., Locksley R. M. Interleukin-4- and interleukin-13-mediated alternatively activated macrophages: roles in homeostasis and disease // Annual Review of Immunology. 2013. Vol. 31. P. 317–343. doi: 10.1146/annurev-immunol-032712-095906.Van Dyken S. J., Locksley R. M. Interleukin-4- and interleukin-13-mediated alternatively activated macrophages: roles in homeostasis and disease. Annu. Rev. Immunol. 2013; 31: 317–343. doi: 10.1146/annurev-immunol-032712-095906.Cua D. J., Sherlock J., Chen Y. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain // Nature. 2003. Vol. 421. P. 744–748. doi: 10.1038/nature01396.Cua D. J., Sherlock J., Chen Y. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature. 2003; 421: 744–748. doi: 10.1038/nature01396.Ivanov II, McKenzie B. S., Zhou L. The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells // Cell. 2006. Vol. 126. P. 1121–1133. doi: 10.1016/j.cell.2006.07.035.Ivanov I. I., McKenzie B. S., Zhou L. The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006; 126: 1121–1133. doi: 10.1016/j.cell.2006.07.035.McGeachy M. J., Cua D. J., Gaffen S. L. The IL-17 family of cytokines in health and disease // Immunity. 2019. Vol. 50. P. 892–906. doi: 10.1016/j.immuni.2019.03.021.McGeachy M. J., Cua D. J., Gaffen S. L. The IL-17 family of cytokines in health and disease. Immunity. 2019; 50: 892–906. doi: 10.1016/j.immuni.2019.03.021.Stockinger B., Omenetti S. The dichotomous nature of T helper 17 cells // Nature Reviews Immunology. 2017. Vol. 17. P. 535–544. doi: 10.1038/nri.2017.50.Stockinger B., Omenetti S. The dichotomous nature of T helper 17 cells. Nature Reviews Immunology. 2017; 17: 535–544. doi: 10.1038/nri.2017.50.Nielsen M. M., Witherden D. A., Havran W. L. γδ T cells in homeostasis and host defence of epithelial barrier tissues // Nature Reviews Immunology. 2017. Vol. 17. P. 733–745. doi: 10.1038/nri.2017.101.Nielsen M. M., Witherden D. A., Havran W. L. γδ T cells in homeostasis and host defence of epithelial barrier tissues. Nature Reviews Immunology. 2017; 17: 733–745. doi: 10.1038/nri.2017.101.Godfrey D. I., Uldrich A. P., McCluskey J. The burgeoning family of unconventional T cells // Nature Immunology. 2015. Vol. 16. P. 1114–1123. doi: 10.1038/ni.3298.Godfrey D. I., Uldrich A. P., McCluskey J. The burgeoning family of unconventional T cells. Nature Immunology. 2015; 16: 1114–1123. doi: 10.1038/ni.3298.Provine N. M., Klenerman P. MAIT cells in health and disease // Annual Review of Immunology. 2020. Vol. 38. P. 203–228. doi: 10.1146/annurev-immunol-080719-015428.Provine N. M., Klenerman P. MAIT cells in health and disease. Annual Review of Immunology. 2020; 38: 203–228. doi: 10.1146/annurev-immunol-080719-015428.Mori L., Lepore M., De Libero G. The immunology of CD1- and MR1-restricted T cells // Annual Review of Immunology. 2016. Vol. 34. P. 479–510. doi: 10.1146/annurev-immunol-032414-112008.Mori L., Lepore M., De Libero G. The immunology of CD1- and MR1-restricted T cells. Annual Review of Immunology. 2016; 34: 479–510. doi: 10.1146/annurev-immunol-032414-112008.

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