mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-TRC-3457mimmun-3457Research ArticleОБЗОРЫREVIEWSКЛЕТКИ ТИМИЧЕСКИЕ РЕЭМИГРАНТЫ В ПРОЦЕССЕ ФУНКЦИОНИРОВАНИЯ ИММУННОЙ СИСТЕМЫTHYMIC REEMIGRANT CELLS IN THE FUNCTIONING OF THE IMMUNE SYSTEMhttps://orcid.org/0000-0002-1756-1782КозловВ. А.KozlovV. A.

Академик РАН, доктор медицинских наук, научный руководитель НИИФКИ, заведующий лабораторией клинической иммунопатологии, заведующий кафедрой иммунологии ИММТ НГУ

Academician of RAS., Prof., Scientific Director RIFСI, Head of the Department of Immunology NNRSU

vakoz40@yandex.ruФедеральное государственное бюджетное научное учреждение «Научно-исследовательский институт фундаментальной и клинической иммунологии» (НИИФКИ), г. Новосибирск, Россия; Федеральное государственное автономное образовательное учреждение высшего образования «Новосибирский национальный исследовательский государственный университет» (НГУ), г. Новосибирск, РоссияРоссияFederal State Budgetary Scientific Institution "Research Institute of Fundamental and Clinical Immunology" (RIFСI), Novosibirsk, Russia; Federal state autonomous educational institution of higher education "Novosibirsk National Research State University" (NNRSU), Novosibirsk, RussiaRussian Federation20192108202600Online First3457Copyright © Козлов В.А., 20192019Козлов В.А.Kozlov V.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/3457

Являясь одним из двух центральным органом иммунной системы организма, тимус является единственным местом воспроизводства Т лимфоцитов. Установлено, что, по существу, после эпифиза, тимус является вторым органов у человека, который подвержен процессу инволюции, причем уже с первого года жизни, когда из тимуса на периферию мигрирует ежедневно достаточное количество Т-клеток в составе CD4+, CD8+ Т-клеток и Treg элементов. Однако оказалось, что на этом не заканчивается миграционная активность органа. Установлено, что в процессе онтогенетического развития тимус представляет собой орган, в который постоянно мигрируют иммунокомпетентные клетки с периферии. Прежде всего к ним относятся предшественники тимоцитов, которые мигрируют из костного мозга. Также в тимус мигрируют с периферии и другие иммунокомпетентные клетки, включая дендритные клетки и В-лимфоциты. Представляет значительный интерес миграция в тимус Т-клеток с периферии, которые перед этим мигрировали, наоборот, из тимуса на периферию. При этом, к старости эти реэмигранты вносят значительный вклад в общую клеточность органа. Эти реэмигранты несут на себе целый функциональных нагрузок, а не являются пассивными жителями тимуса.

Показано, что принимают участие в процессах как в позитивной, так и негативной селекции. Т-клетки памяти после миграции в тимус продолжают там оставаться в течение неопределенного времени. Они оказывают поддержку функциональной активности эпителиальных клеток тимуса.  Реэмигрирующие в тимус зрелые Treg тормозят производство новых регуляторных клеток, тем самым принимая участие также в процессе инволюции тимуса. Несомненно, что обратные тимические реэмигранты вносят свой вклад в иммунопатогенез многих иммунокомпрометированных заболеваний. Оценка показателей функции тимуса в раннем возрасте даст возможность раннего диагностирования нарушений функционирования тимуса, а это значит и всего иммуно-структурного гомеостаза с последующим проведением терапевтических мероприятий в отношении коррекции нарушений функций тимуса.

As one of the two central organs of the body's immune system, the thymus is the only place where T lymphocytes are produced. It has been established that, in fact, after the pineal gland, the thymus is the second organ in humans that undergoes involution, starting from the first year of life, when a sufficient number of CD4+, CD8+, and Treg cells migrate from the thymus to the periphery on a daily basis. However, it has been discovered that the organ's migration activity does not end there. It has been established that during ontogenetic development, the thymus is an organ into which immunocompetent cells from the periphery constantly migrate. First of all, these include thymocyte precursors that migrate from the bone marrow. Other immunocompetent cells, including dendritic cells and B-lymphocytes, also migrate from the periphery to the thymus. Of particular interest is the migration of T cells from the periphery to the thymus, which had previously migrated from the thymus to the periphery. These re-emigrants contribute significantly to the overall cellularity of the organ as we age. These re-emigrants carry a whole functional load, and are not passive residents of the thymus. It has been shown that they take part in both positive and negative selection processes. Memory T cells continue to remain in the thymus for an indefinite period of time after migration. They provide support for the functional activity of thymic epithelial cells. Mature Treg cells that re-emigrate to the thymus inhibit the production of new regulatory cells, thereby also participating in the process of thymic involution. There is no doubt that reverse thymic reemigrants contribute to the immunopathogenesis of many immunocompromised diseases.

тимусстарениемиграция Т-клетокТ-регуляторные клеткитимические реэмигрантыиммунный гомеостазиммунопатология.thymusagingT-cell migrationT-regulatory cellsthymic reemigrantsimmune homeostasisimmunopathology.ReferencesМиллер, Дж. Биология тимуса / Дж. Миллер, П. Дукор; пер. с нем. В.И. Самойлова; под ред. С. В. Скурковича. М.: Мир, - 1967. - 112 с.Миллер, Дж. Биология тимуса / Дж. Миллер, П. Дукор; пер. с нем. В.И. Самойлова; под ред. С. В. Скурковича. М.: Мир, - 1967. - 112 с.Agus D.B., Surh C.D., Sprent J. Reentry of T cells to the adult thymus is restricted to activated T cells. J Exp Med., 1991, Vol. 173, no 5, pp. 1039-1046.Agus D.B., Surh C.D., Sprent J. Reentry of T cells to the adult thymus is restricted to activated T cells. J Exp Med., 1991, Vol. 173, no 5, pp. 1039-1046.Ayasoufi K., Fan R, Valujskikh A Depletion-resistant CD4 T cells enhance thymopoiesis during Lymphopenia. Am J Transplant., 2017, Vol. 17, no. 8. Pp. 2008–2019.Ayasoufi K., Fan R, Valujskikh A Depletion-resistant CD4 T cells enhance thymopoiesis during Lymphopenia. Am J Transplant., 2017, Vol. 17, no. 8. Pp. 2008–2019.Bosco N., Kirberg J., Ceredig R., Agenès F. Peripheral T cells in the thymus: have they just lost their way or do they do something?. Immunol Cell Biol., 2009, Vol. 87, no. 1, pp. 50-57.Bosco N., Kirberg J., Ceredig R., Agenès F. Peripheral T cells in the thymus: have they just lost their way or do they do something?. Immunol Cell Biol., 2009, Vol. 87, no. 1, pp. 50-57.Charaix J, Borelli A, Santamaria JC, et al. Recirculating Foxp3+ regulatory T cells are restimulated in the thymus under Aire control. Cell Mol Life Sci., 2022, Vol. 79, no. 7, pp. 355.Charaix J, Borelli A, Santamaria JC, et al. Recirculating Foxp3+ regulatory T cells are restimulated in the thymus under Aire control. Cell Mol Life Sci., 2022, Vol. 79, no. 7, pp. 355.Cowan J.E., Baik S., McCarthy N.I., Parnell S.M., White A.J., Jenkinson W.E., Anderson G. Aire controls the recirculation of murine Foxp3+ regulatory T-cells back to the thymus Eur. J. Immunol., 2018, Vol. 48, no. 5, pp. 844–854.Cowan J.E., Baik S., McCarthy N.I., Parnell S.M., White A.J., Jenkinson W.E., Anderson G. Aire controls the recirculation of murine Foxp3+ regulatory T-cells back to the thymus Eur. J. Immunol., 2018, Vol. 48, no. 5, pp. 844–854.Cowan J.E., McCarthy N.I., Anderson G. CCR7 Controls Thymus Recirculation, but Not Production and Emigration, of Foxp3+ T Cells. Cell Rep., 2016, Vol. 4, no. 5, pp. 1041–1048.Cowan J.E., McCarthy N.I., Anderson G. CCR7 Controls Thymus Recirculation, but Not Production and Emigration, of Foxp3+ T Cells. Cell Rep., 2016, Vol. 4, no. 5, pp. 1041–1048.Dardenne M., Smaniotto S., de Mello-Coelho V., Villa-Verde D.M., Savino W. Growth hormone modulates migration of developing T cells. Ann N Y Acad Sci., 2009, Vol. 1153, pp. 1-5.Dardenne M., Smaniotto S., de Mello-Coelho V., Villa-Verde D.M., Savino W. Growth hormone modulates migration of developing T cells. Ann N Y Acad Sci., 2009, Vol. 1153, pp. 1-5.Darrigues J., Santamaria J. C., Galindo-Albarrán A., Robey E. A., Joffre O. P., van Meerwijk J. P. M., Romagnoli P. Robust intrathymic development of regulatory T cells in young NOD mice is rapidly restrained by recirculating cells. European journal of immunology, 2221, Vol. 51, no. 3, pp. 580–593.Darrigues J., Santamaria J. C., Galindo-Albarrán A., Robey E. A., Joffre O. P., van Meerwijk J. P. M., Romagnoli P. Robust intrathymic development of regulatory T cells in young NOD mice is rapidly restrained by recirculating cells. European journal of immunology, 2221, Vol. 51, no. 3, pp. 580–593.Dumont F. J., Barrois R., Jacobson E. B. Migration of peripheral T and B cells into the thymus of aging (NZB X SJL)F1 female mice. Cellular immunology, 1984, Vol. 83, no. 2, pp. 292–301.Dumont F. J., Barrois R., Jacobson E. B. Migration of peripheral T and B cells into the thymus of aging (NZB X SJL)F1 female mice. Cellular immunology, 1984, Vol. 83, no. 2, pp. 292–301.Edelmann S. L., Marconi P., Brocker T. Peripheral T cells re-enter the thymus and interfere with central tolerance induction. Journal of immunology, 2011, Vol. 186, no. 10, pp. 5612–5619.Edelmann S. L., Marconi P., Brocker T. Peripheral T cells re-enter the thymus and interfere with central tolerance induction. Journal of immunology, 2011, Vol. 186, no. 10, pp. 5612–5619.Fink P.J., Bevan M.J., Weissman I.L. Thymic cytotoxic T lymphocytes are primed in vivo to minor histocompatibility antigens. J Exp Med, 1984, Vol. 159, no. 2, pp. 436–451.Fink P.J., Bevan M.J., Weissman I.L. Thymic cytotoxic T lymphocytes are primed in vivo to minor histocompatibility antigens. J Exp Med, 1984, Vol. 159, no. 2, pp. 436–451.Gao Y.N., Pei X.Y., Jin R., Yin C., Shen H., Sun X.Y., Ge Q., Zhang Y. Suspension of thymic emigration promotes the maintenance of antigen-specific memory T cells and the recall responses. Bioch Biophys Res Commun, 2014, Vol. 454, no.2, pp. 275–281.Gao Y.N., Pei X.Y., Jin R., Yin C., Shen H., Sun X.Y., Ge Q., Zhang Y. Suspension of thymic emigration promotes the maintenance of antigen-specific memory T cells and the recall responses. Bioch Biophys Res Commun, 2014, Vol. 454, no.2, pp. 275–281.Gopinathan R., DePaz H.A., Oluwole O.O., Engelstad K., Ali A.O., Garrovillo M., Fawwaz R.A., Wang T.S., Hardy M.A., Oluwole S.F. Mechanisms of acquired tolerance induced by adoptive transfer of MHC-specific alloreactive T cells: effector T cells migrate to the thymus. Transplant Proc., 2001, Vol. Vol. 33, no. 1-2, pp. 92.Gopinathan R., DePaz H.A., Oluwole O.O., Engelstad K., Ali A.O., Garrovillo M., Fawwaz R.A., Wang T.S., Hardy M.A., Oluwole S.F. Mechanisms of acquired tolerance induced by adoptive transfer of MHC-specific alloreactive T cells: effector T cells migrate to the thymus. Transplant Proc., 2001, Vol. Vol. 33, no. 1-2, pp. 92.Hale J.S., Boursalian T.E., Turk G.L., Fink P.J. Thymic output in aged mice. Proc. Natl. Acad. Sci. U. S. A., 2006, Vol. 103, no. 22, pp. 8447–8452.Hale J.S., Boursalian T.E., Turk G.L., Fink P.J. Thymic output in aged mice. Proc. Natl. Acad. Sci. U. S. A., 2006, Vol. 103, no. 22, pp. 8447–8452.Hale J.S., Fink P.J. Back to the Thymus: Peripheral T Cells Come Home. Immunol Cell Biol., 2009, Vol. 87, no. 1, pp. 58–64.Hale J.S., Fink P.J. Back to the Thymus: Peripheral T Cells Come Home. Immunol Cell Biol., 2009, Vol. 87, no. 1, pp. 58–64.Hirokawa K., Utsuyama M., Sado T. Immunohistological analysis of immigration of thymocyte-precursors into the thymus: evidence for immigration of peripheral T cells into the thymic medulla. Cell Immunol., 1989, Vol. 119, no. 1, pp. 160-170.Hirokawa K., Utsuyama M., Sado T. Immunohistological analysis of immigration of thymocyte-precursors into the thymus: evidence for immigration of peripheral T cells into the thymic medulla. Cell Immunol., 1989, Vol. 119, no. 1, pp. 160-170.Kirberg J., Bosco N., Deloulme J.C., Ceredig R., Agenès F. Peripheral T lymphocytes recirculating back into the thymus can mediate thymocyte positive selection. J Immunol., 2008, Vol. 181, no. 2, pp. 1207-1214.Kirberg J., Bosco N., Deloulme J.C., Ceredig R., Agenès F. Peripheral T lymphocytes recirculating back into the thymus can mediate thymocyte positive selection. J Immunol., 2008, Vol. 181, no. 2, pp. 1207-1214.Lemarquis A.L., Kousa A.I., Argyropoulos K.V., Jahn L., Gipson B., Pierce J., Serrano-Marin L., Victor K., Kanno Y., Girotra N.N., Andrlova H., Tsai J., Velardi E., Sharma R., Grassmann S., Ekwall O., Goldstone A.B., Dudakov J.A., DeWolf S., van den Brink M.R.M. Recirculating regulatory T cells mediate thymic regeneration through amphiregulin following damage. Immunity, 2025, Vol. 58, no. 2, pp. 397-411.e6.Lemarquis A.L., Kousa A.I., Argyropoulos K.V., Jahn L., Gipson B., Pierce J., Serrano-Marin L., Victor K., Kanno Y., Girotra N.N., Andrlova H., Tsai J., Velardi E., Sharma R., Grassmann S., Ekwall O., Goldstone A.B., Dudakov J.A., DeWolf S., van den Brink M.R.M. Recirculating regulatory T cells mediate thymic regeneration through amphiregulin following damage. Immunity, 2025, Vol. 58, no. 2, pp. 397-411.e6.Levinson A.I., Song D., Gaulton G., Zheng Y. The intrathymic pathogenesis of myasthenia gravis. Clin Dev Immunol, 2004, Vol. 11, no. 3-4, pp. 215–220.Levinson A.I., Song D., Gaulton G., Zheng Y. The intrathymic pathogenesis of myasthenia gravis. Clin Dev Immunol, 2004, Vol. 11, no. 3-4, pp. 215–220.Losada-Barragán M., Umaña-Pérez A., Cuervo-Escobar S., Berbert L.R., Porrozzi R., Morgado F.N., Mendes-da-Cruz D.A., Savino W., Sánchez-Gómez M., Cuervo P. Protein malnutrition promotes dysregulation of molecules involved in T cell migration in the thymus of mice infected with Leishmania infantum. Sci Rep., 2017, Vol. 7, pp. 45991.Losada-Barragán M., Umaña-Pérez A., Cuervo-Escobar S., Berbert L.R., Porrozzi R., Morgado F.N., Mendes-da-Cruz D.A., Savino W., Sánchez-Gómez M., Cuervo P. Protein malnutrition promotes dysregulation of molecules involved in T cell migration in the thymus of mice infected with Leishmania infantum. Sci Rep., 2017, Vol. 7, pp. 45991.McCarthy N.I., Cowan J.E., Nakamura K., Bacon A., Baik S., White A.J., Parnell S.M., Jenkinson E.J., Jenkinson W.E., Anderson G. Osteoprotegerin-Mediated Homeostasis of Rank+ Thymic Epithelial Cells Does Not Limit Foxp3+ Regulatory T Cell Development. J Immunol., 2015, Vol. 195, no. 6, pp. 2675-2682.McCarthy N.I., Cowan J.E., Nakamura K., Bacon A., Baik S., White A.J., Parnell S.M., Jenkinson E.J., Jenkinson W.E., Anderson G. Osteoprotegerin-Mediated Homeostasis of Rank+ Thymic Epithelial Cells Does Not Limit Foxp3+ Regulatory T Cell Development. J Immunol., 2015, Vol. 195, no. 6, pp. 2675-2682.Michie S.A., Kirkratrick E.A., Rouse R.V. Rare peripheral T cells migrate to and normal mouse thymus. J Exp Med, 1988, Vol. 168, no. 5, pp. 1929-1934.Michie S.A., Kirkratrick E.A., Rouse R.V. Rare peripheral T cells migrate to and normal mouse thymus. J Exp Med, 1988, Vol. 168, no. 5, pp. 1929-1934.Michie S.A., Streeter P.R., Butcher E.C., Rouse R.V. L-selectin and alpha 4 beta 7 integrin homing receptor pathways mediate peripheral lymphocyte traffic to AKR mouse hyperplastic thymus. Am J Pathol., 1995, Vol. 147, no. 2, pp. 412-421.Michie S.A., Streeter P.R., Butcher E.C., Rouse R.V. L-selectin and alpha 4 beta 7 integrin homing receptor pathways mediate peripheral lymphocyte traffic to AKR mouse hyperplastic thymus. Am J Pathol., 1995, Vol. 147, no. 2, pp. 412-421.Naparstek Y., Holoshitz J., Eisenstein S., Reshef T., Rappaport S., Chemke J., Avraham Ben-Nun A., Cohen I.R. Effector T lymphocyte line cells migrate to the thymus and persist there. Nature, 1982, Vol. 300, pp. 262–264.Naparstek Y., Holoshitz J., Eisenstein S., Reshef T., Rappaport S., Chemke J., Avraham Ben-Nun A., Cohen I.R. Effector T lymphocyte line cells migrate to the thymus and persist there. Nature, 1982, Vol. 300, pp. 262–264.Nikolouli E., Elfaki Y., Herppich S., Schelmbauer C., Delacher M., Falk C., Mufazalov I.A., Waisman A., Feuerer M., Huehn J.. Recirculating IL-1R2+ Tregs fine-tune intrathymic Treg development under inflammatory conditions. Cell Mol Immunol., 2021, Vol. 18, no. 1, pp. 182-193.Nikolouli E., Elfaki Y., Herppich S., Schelmbauer C., Delacher M., Falk C., Mufazalov I.A., Waisman A., Feuerer M., Huehn J.. Recirculating IL-1R2+ Tregs fine-tune intrathymic Treg development under inflammatory conditions. Cell Mol Immunol., 2021, Vol. 18, no. 1, pp. 182-193.Nobrega C., Nunes-Alves C., Cerqueira-Rodrigues B., Roque S., Barreira-Silva P., Behar S.M., Correia-Neves M. T cells home to the thymus and control infection. J Immunol., 2013, Vol. 190, no. 4, pp. 1646-1658.Nobrega C., Nunes-Alves C., Cerqueira-Rodrigues B., Roque S., Barreira-Silva P., Behar S.M., Correia-Neves M. T cells home to the thymus and control infection. J Immunol., 2013, Vol. 190, no. 4, pp. 1646-1658.Peligero-Cruz C., Givony T., Sebé-Pedrós A., Dobeš J., Kadouri N., Nevo S., Roncato F., Alon R., Goldfarb Y., Abramson J. IL18 signaling promotes homing of mature Tregs into the thymus. Elife., 2020, Vol. 9, pp. e58213.Peligero-Cruz C., Givony T., Sebé-Pedrós A., Dobeš J., Kadouri N., Nevo S., Roncato F., Alon R., Goldfarb Y., Abramson J. IL18 signaling promotes homing of mature Tregs into the thymus. Elife., 2020, Vol. 9, pp. e58213.Santamaria J., Darrigues J., van Meerwijk J.P.M., Romagnoli P. Antigen-presenting cells and T-lymphocytes homing to the thymus shape T cell development. Immunol Lett., 2018, Vol. 204, pp. 9-15.Santamaria J., Darrigues J., van Meerwijk J.P.M., Romagnoli P. Antigen-presenting cells and T-lymphocytes homing to the thymus shape T cell development. Immunol Lett., 2018, Vol. 204, pp. 9-15.Santamaria J.C., Borelli A., Irla M. Regulatory T Cell Heterogeneity in the Thymus: Impact on Their Functional Activities. Front. Immunol., 2021, Vol. 12, pp. 643153.Santamaria J.C., Borelli A., Irla M. Regulatory T Cell Heterogeneity in the Thymus: Impact on Their Functional Activities. Front. Immunol., 2021, Vol. 12, pp. 643153.Santamaria J.C., Vuillier S., Galindo-Albarrán A.O., Castan S., Detraves C., Joffre O.P., Romagnoli P., van Meerwijk J.P.M. The type 1 diabetes susceptibility locus Idd5 favours robust neonatal development of highly autoreactive regulatory T cells in the NOD mouse. Front Immunol., 2024, Vol. 15, pp. 1358459.Santamaria J.C., Vuillier S., Galindo-Albarrán A.O., Castan S., Detraves C., Joffre O.P., Romagnoli P., van Meerwijk J.P.M. The type 1 diabetes susceptibility locus Idd5 favours robust neonatal development of highly autoreactive regulatory T cells in the NOD mouse. Front Immunol., 2024, Vol. 15, pp. 1358459.Smaniotto S., Ribeiro-Carvalho M.M., Dardenne M., Savino W., de Mello-Coelho V.. Growth hormone stimulates the selective trafficking of thymic CD4+CD8- emigrants to peripheral lymphoid organs. Neuroimmunomodulation, 2004, Vol. 11, no. 5, pp. 299-306.Smaniotto S., Ribeiro-Carvalho M.M., Dardenne M., Savino W., de Mello-Coelho V.. Growth hormone stimulates the selective trafficking of thymic CD4+CD8- emigrants to peripheral lymphoid organs. Neuroimmunomodulation, 2004, Vol. 11, no. 5, pp. 299-306.Sprent J., Surh C.D.. Re-entry of mature T cells to the thymus: an epiphenomenon? Immunol Cell Biol., 2009, Vol. 87, no. 1, pp. 46-49.Sprent J., Surh C.D.. Re-entry of mature T cells to the thymus: an epiphenomenon? Immunol Cell Biol., 2009, Vol. 87, no. 1, pp. 46-49.Surh C.D., Ernst B., Sprent J. Growth of epithelial cells in the thymic medulla is under the control of mature T cells. J Exp Med., 1992, Vol. 176, no. 2, pp. 611-616Surh C.D., Ernst B., Sprent J. Growth of epithelial cells in the thymic medulla is under the control of mature T cells. J Exp Med., 1992, Vol. 176, no. 2, pp. 611-616Surh C.D., Sprent J., Webb S.R. Exclusion of circulating T cells from the thymus does not apply in the neonatal period. J Exp Med., 1993, Vol. 177, no. 2, pp. 379-385.Surh C.D., Sprent J., Webb S.R. Exclusion of circulating T cells from the thymus does not apply in the neonatal period. J Exp Med., 1993, Vol. 177, no. 2, pp. 379-385.Taub D.D., Tsarfaty G., Lloyd A.R., Durum S.K., Longo D.L., Murphy W.J. Growth hormone promotes human T cell adhesion and migration to both human and murine matrix proteins in vitro and directly promotes xenogeneic engraftment. J Clin Invest., 1994, Vol. 94, no. 1, pp. 293-300.Taub D.D., Tsarfaty G., Lloyd A.R., Durum S.K., Longo D.L., Murphy W.J. Growth hormone promotes human T cell adhesion and migration to both human and murine matrix proteins in vitro and directly promotes xenogeneic engraftment. J Clin Invest., 1994, Vol. 94, no. 1, pp. 293-300.Thiault N., Darrigues J., Adoue V., Gros M., Binet B., Perals C., Leobon B., Fazilleau N., Joffre O.P., Robey E.A., van Meerwijk J.P., Romagnoli P. Peripheral regulatory T lymphocytes recirculating to the thymus suppress the development of their precursors. Nat Immunol., 2015, Vol. 16, no. 6, pp. 628-634.Thiault N., Darrigues J., Adoue V., Gros M., Binet B., Perals C., Leobon B., Fazilleau N., Joffre O.P., Robey E.A., van Meerwijk J.P., Romagnoli P. Peripheral regulatory T lymphocytes recirculating to the thymus suppress the development of their precursors. Nat Immunol., 2015, Vol. 16, no. 6, pp. 628-634.Tian C., Bagley J., Forman D., Iacomini J. Induction of central tolerance by mature T cells. J Immunol., 2004, Vol. 173, no. 12, pp. 7217-7222.Tian C., Bagley J., Forman D., Iacomini J. Induction of central tolerance by mature T cells. J Immunol., 2004, Vol. 173, no. 12, pp. 7217-7222.Tong Q., Yao L., Su M., Yang Y.G., Sun L.. Thymocyte migration and emigration. Immunol Lett., 2024, Vol. 267, pp. 106861.Tong Q., Yao L., Su M., Yang Y.G., Sun L.. Thymocyte migration and emigration. Immunol Lett., 2024, Vol. 267, pp. 106861.Westermann J., Smith T., Peters U., Tschernig T., Pabst R., Steinhoff G., Sparshott S.M., Bell E.B. Both activated and nonactivated leukocytes from the periphery continuously enter the thymic medulla of adult rats: phenotypes, sources and magnitude of traffic. Eur J Immunol., 1996, Vol. 26, no. 8, pp. 1866-1874.Westermann J., Smith T., Peters U., Tschernig T., Pabst R., Steinhoff G., Sparshott S.M., Bell E.B. Both activated and nonactivated leukocytes from the periphery continuously enter the thymic medulla of adult rats: phenotypes, sources and magnitude of traffic. Eur J Immunol., 1996, Vol. 26, no. 8, pp. 1866-1874.Wu H., Li X., Zhou C., Yu Q., Ge S., Pan Z., Zhao Y., Xia S., Zhou X., Liu X., Wang H., Shao Q. Circulating mature dendritic cells homing to the thymus promote thymic epithelial cells involution via the Jagged1/Notch3 axis. Cell Death Discov., 2021, Vol. 7, no. 1, pp. 225.Wu H., Li X., Zhou C., Yu Q., Ge S., Pan Z., Zhao Y., Xia S., Zhou X., Liu X., Wang H., Shao Q. Circulating mature dendritic cells homing to the thymus promote thymic epithelial cells involution via the Jagged1/Notch3 axis. Cell Death Discov., 2021, Vol. 7, no. 1, pp. 225.Yang E., Zou T., Leichner T.M., Zhang S.L., Kambayashi T. Both retention and recirculation contribute to long-lived regulatory T-cell accumulation in the thymus. Eur J Immunol., 2014, Vol. 44, no. 9, pp. 2712-2720.Yang E., Zou T., Leichner T.M., Zhang S.L., Kambayashi T. Both retention and recirculation contribute to long-lived regulatory T-cell accumulation in the thymus. Eur J Immunol., 2014, Vol. 44, no. 9, pp. 2712-2720.Yin C., Pei X.Y., Shen H., Gao Y.N., Sun X.Y., Wang W., Ge Q., Zhang Y. Thymic homing of activated CD4+ T cells induces degeneration of the thymic epithelium through excessive RANK signaling. Sci Rep., 2017, Vol. 7, no. 1, pp. 2421.Yin C., Pei X.Y., Shen H., Gao Y.N., Sun X.Y., Wang W., Ge Q., Zhang Y. Thymic homing of activated CD4+ T cells induces degeneration of the thymic epithelium through excessive RANK signaling. Sci Rep., 2017, Vol. 7, no. 1, pp. 2421.Zhan Y., Bourges D., Dromey J.A., Harrison L.C., Lew A.M. The origin of thymic CD4+CD25+ regulatory T cells and their co-stimulatory requirements are determined after elimination of recirculating peripheral CD4+ cells. Int Immunol., 2007, Vol. 19, no. 4, pp. 455-463.Zhan Y., Bourges D., Dromey J.A., Harrison L.C., Lew A.M. The origin of thymic CD4+CD25+ regulatory T cells and their co-stimulatory requirements are determined after elimination of recirculating peripheral CD4+ cells. Int Immunol., 2007, Vol. 19, no. 4, pp. 455-463.

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