Effects of interaction between circulating CD4+CCR6+ T cells and B-lymphocytes

Abstract

Introduction. The chemokine receptor CCR6 is expressed on a portion of mature circulating CD4+CD45RO+-T-lymphocytes and gives them the potential to migrate into Peyer’s patches, inflamed gastrointestinal mucosa, and skin. The group of CD4+CD45RO+CCR6+ blood T-lymphocytes includes cells with various functions, in particular, pro-inflammatory T-helper-17 (Th17) and Th1, as well as anti-inflammatory FoxP3+ regulatory T cells. In addition, this group includes a small number of cells with the phenotype of follicular T-helper cells (fTh), professional stimulators of the humoral immune response.

The aim of the study was to evaluate the ability of blood CD4+CCR6+ T cells to help B-lymphocytes, as well as the response of T-helper subgroups to interaction with B cells.

Material and methods. Total pool of CD4+ T cells, CD4+CD45RO+CCR6+ T cells, or naive T-helper cells (nTh) were isolated from the blood of healthy adult donors, cultured with allogeneic B lymphocytes, and immunoglobulin production and T cell response were evaluated.

Results. It has been shown that mature CD4+CCR6+ T cells stimulate the production of IgM and IgG in mixed culture of T and B lymphocytes more strongly than nTh or total pool of CD4+ T cells. The interaction of CD4+CCR6+ T cells with B lymphocytes led to the expansion of Th17 and Th1/Th17 cells in culture without a noticeable increase in the number of Th1 and fTh cells. At the same time, nTh or undivided CD4+ T cells, activated by contact with allogeneic B lymphocytes, preferentially differentiate into fTh-like cells.

Conclusion. CD4+CCR6+ T cells effectively help B-lymphocytes, which is accompanied by the expansion of Th17 and Th1/Th17 cells, but not Th1 and fTh cells.

Keywords:immune response; follicular T-helper cells; T-helper-17 cells; B cells; antibody production

For citation: Talayev V.Yu., Voronina E.V., Svetlova M.V., Zaichenko I.Ye., Babaykina О.N. Effects of interaction between circulating CD4+CCR6+ T cells and B-lymphocytes. Immunologiya. 2022; 43 (3): 266–76. DOI: https://doi.org/10.33029/0206-4952-2022-43-3-266-276

Funding. The study was supported by RFBR, project No. 18-015-00028.

Conflict of interests. The authors declare no conflict of interests.

Authors contribution. Study design, article writing – Talayev V.Yu.; purification, cultivation and staining of cells – Voronina E.V.; cell purification and flow cytometry – Svetlova M.V.; cultivation and staining of cells, ELISA – Zaichenko I.Ye.; cell cultivation, ELISA – Babaykina O.N.

References

1. Wang C., Kang S.G., Lee J., Sun Z., Kim C.H. The roles of CCR6 in migration of Th17 cells and regulation of effector T-cell balance in the gut. Mucosal Immunol. 2009; 2: 173–83. DOI: https://doi.org/10.1038/mi.2008.84

2. Villablanca E.J., Cassani B., von Andrian U.H., Mora J.R. Blocking lymphocyte localization to the gastrointestinal mucosa as a therapeutic strategy for inflammatory bowel diseases. Gastroenterology. 2011; 140: 1776–84. DOI: https://doi.org/10.1053/j.gastro.2011.02.015

3. Wu Y.Y., Tsai H.F., Lin W.C., Hsu P.I., Shun C.T., Wu M.S., Hsu P.N. Upregulation of CCL20 and recruitment of CCR6+ gastric infiltrating lymphocytes in Helicobacter pylori gastritis. Infect. Immun. 2007; 75: 4357–63. DOI: https://doi.org/10.1128/IAI.01660-06

4. Harper E.G., Guo C., Rizzo H., Lillis J.V., Kurtz S.E., Skorcheva I., et al. Th17 cytokines stimulate CCL20 expression in keratinocytes in vitro and in vivo: implications for psoriasis pathogenesis. J. Invest. Dermatol. 2009; 129 (9): 2175–83. DOI: https://doi.org/10.1038/jid. 2009.65

5. Singh S.P., Zhang H.H., Tsang H., Gardina P.J., Myers T.G., Nagarajan V., et al. PLZF regulates CCR6 and is critical for the acquisition and maintenance of the Th17 phenotype in human cells. J. Immunol. 2015; 194: 4350–61. DOI: https://doi.org/10.4049/jimmunol.1401093

6. Talaev V.Yu., Svetlova M.V., Zaichenko I.E., Voronina E.V., Babaykina O.N., Neumoina N.V., et al. Cytokine profile of CCR6+ T-helpers isolated from the blood of patients with peptic ulcer associated with Helicobacter pylori infection. Sovremennye tekhnologii v meditsine. 2020; 12: 33–40. DOI: https://doi.org/10.17691/stm2020.12.3.04

7. Mazzoni A., Maggi L., Liotta F., Cosmi L., Annunziato F. Biological and clinical significance of T helper 17 cell plasticity. Immunology. 2019; 158 (4): 287–95. DOI: https://doi.org/10.1111/imm.13124

8. Kleinewietfeld M., Puentes F., Borsellino G., Battistini L., Rötzschke O., Falk K. CCR6 expression defines regulatory effector/memory-like cells within the CD25+CD4+ T-cell subset. Blood. 2005; 105: 2877–86. DOI: https://doi.org/10.1182/blood-2004-07-2505

9. Talaev V.Y., Talaeva M.V., Voronina E.V., Zaichenko I.Y., Neumoina N.V., Perfilova K.M., Babaykina O.N. Chemokine receptor expression on peripheral blood T-helper cells in Helicobacter pylori-associated diseases: chronic gastroduodenitis and peptic ulcer disease. Infektsiya i immunitet. 2019; 9: 295–303. DOI: https://doi.org/10.15789/2220-7619-2019-2-295-303 (in Russian)

10. Ma C.S., Deenick E.K., Batten M., Tangye S.G. The origins, function, and regulation of T follicular helper cells. J. Exp. Med. 2012; 209: 1241–53. DOI: https://doi.org/10.1084/jem.20120994

11. Fazilleau N., Mark L., McHeyzer-Williams L.J., McHeyzer-Williams M.H. Follicular helper T cells: lineage and location. Immunity. 2009; 30: 324–35. DOI: https://doi.org/10.1016/j.immuni.2009.03.003

12. McHeyzer-Williams L., Pelletier N., Mark L., Fazilleau N., McHeyzer-Williams M.G. Folicular helper T-cells as cognate regulator of B cell immunity. Curr. Opin. Immunol. 2009; 21: 266–73. DOI: https://doi.org/10.1016/j.coi.2009.05.010

13. Wang C., Hillsamer P., Kim C.H. Phenotype, effector function, and tissue localization of PD-1-expressing human follicular helper T cell subsets. BMC Immunol. 2011; 12: 53. DOI: https://doi.org/10.1186/1471-2172-12-53

14. Crotty S. Follicular helper CD4 T cells (TFH). Annu. Rev. Immunol. 2011; 29: 621–63. DOI: https://doi.org/10.1146/annurev-immunol-031210-101400

15. Annunziato F., Romagnani S. Heterogeneity of human effector CD4+ T cells. Arthritis Res. Ther. 2009; 11: 257. DOI: https://doi.org/10.1186/ar2843

16. Mosmann T.R., Coffman R.L. Two types of mouse helper T-cell clone: implications for immune regulation. Immunol. Today. 1987; 8: 223–7. DOI: https://doi.org/10.1016/0167-5699(87)90171-X

17. Tsuji M., Komatsu N., Kawamoto S., Suzuki K., Kanagawa O., Honjo T., Hori S., Fagarasan S. Preferential generation of follicular B helper T cells from Foxp3+ T cells in gut Peyer’s patches. Science. 2009; 323: 1488–92. DOI: https://doi.org/10.1126/science.1169152

18. Cong Y., Feng T., Fujihashi K., Schoeb T.R., Elson C.O. A dominant, coordinated T regulatory cell-IgA response to the intestinal microbiota. Proc. Natl Acad. Sci. USA. 2009; 106: 19 256–61. DOI: https://doi.org/10.1073/pnas.0812681106

19. Dullaers M., Li D., Xue Y., Ni L., Gayet In., Morita R., Ueno H., Palucka K.A., Banchereau J., Oh S. A T cell-dependent mechanism for the induction of human mucosal homing immunoglobulin A-secreting plasmablasts. Immunity. 2009; 30: 120–9. DOI: https://doi.org/10.1016/j.immuni.2008.11.008

20. Annunziato F., Cosmi L., Santarlasci V., et al. Phenotypic and functional features of human Th17 cells. J. Exp. Med. 2007; 204: 1849–61. DOI: https://doi.org/10.1084/jem.20070663

21. Damsker J.M., Hansen A.M., Caspi R.R. Th1 and Th17 cells: adversaries and collaborators. Ann. N. Y. Acad. Sci. 2010; 1183: 211–21. DOI: https://doi.org/10.1111/j.1749-6632.2009.05133.x

22. Murphy K.M., Stockinger B. Effector T cell plasticity: flexibility in the face of changing circumstances. Nat. Immunol. 2010; 11: 674–80. DOI: https://doi.org/10.1038/ni.1899

23. Hirota К., Turner J., Villa M., Duarte J.H., Demengeot J., Steinmetz O.M., Stockinger B. TH17 cell plasticity in Peyer’s patches is responsible for induction of T cell-dependent IgA responses. Nat. Immunol. 2013; 14: 372–9. DOI: https://doi.org/10.1038/ni.2552

24. Hartlehnert M., Börsch A.L., Li X., Burmeister M., Gerwien H., Schafflick D., et al. Bcl6 controls meningeal Th17-B cell interaction in murine neuroinflammation. Proc. Natl Acad. Sci. USA. 2021; 118: e2023174118. DOI: https://doi.org/10.1073/pnas.2023174118

25. Talaev V.Yu., Plekhanova M.V., Voronina E. V., Babaykina O.N. Maturation of T follicular helper cells in vitro. Immunologiya. 2015; 36 (6): 336–43 (in Russian)

26. Byazrova M.G., Astakhova E.A., Spiridonova A.B., Vasil’eva Yu.V., Prilipov A.G., Filatov A.V IL-21/CD40L stimulation of human B-lymphocytes in vitro and their characteristics. Immunologiya. 2020; 41 (6): 501–10. DOI: https://doi.org/10.33029/0206-4952-2020-41-6-501-510 (in Russian)

27. Astakhova E.A., Frolov E.A., Shilkina A.B., Byazrova M.G., Latysheva E.A., Latysheva T.V., Filatov A.V Stimulation of B cells in the IL-21/CD40L system in healthy donors and in patients with common variable immunodeficiency. Immunologiya. 2021; 41 (6): 631–40. DOI: https://doi.org/10.33029/0206-4952-2021-42-6-631-640 (in Russian)

28. Bounia C.A., Liossis S.C. B cell depletion treatment decreases Th17 cells in patients with rheumatoid arthritis. Clin. Immunol. 2021; 233: 108877. DOI: https://doi.org/10.1016/j.clim.2021.108877

EDITOR-IN-CHIEF
EDITOR-IN-CHIEF
Musa R. Khaitov

Corresponding member of Russian Academy of Sciences, MD, Professor, Director of the NRC Institute of Immunology FMBA of Russia

Вскрытие
Medicine today

II Всероссийская конференция с международным участием "Воспаление глаза" 12 ноября 2022 года, Москва Воспалительные заболевания глаза - широко распространенная и многогранная проблема, с которой может столкнуться в своей практике любой специалист. Найти оптимальные алгоритмы...

Масштабное событие в области дерматовенерологии и косметологии - II конференция InteDeCo 2022 "Интегративная дерматовенерология и косметология. Новые стандарты взаимодействия" - состоится 16-17 декабря 2022 года. Программа мероприятия пройдет на современной...

VIII Московский Городской Съезд педиатров с межрегиональным и международным участием "Трудный диагноз в педиатрии" Приглашаем педиатров, детских эндокринологов, реаниматологов, гинекологов, неонатологов, кардиологов, хирургов, урологов, психологов, специалистов по лучевой...


JOURNALS of «GEOTAR-Media»