THE INFLUENCE OF IL-7 AND IL-15 ON T-REGULATORY CELLS OF DONORS AND PATIENTS WITH RHEUMATOID ARTHRITIS IN VITRO

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The aim of this study was to assess the infl uence of homeostatic factors IL-7 and IL-15, that induced homeostatic proliferation (HP), on the phenotypic characteristics of T-regulatory cells (Treg) from healthy donors and patients with rheumatoid arthritis (RA) in vitro. Analysis of Treg phenotype was performed by fl ow cytometry, using Foxp3, CD127, CD4 and CD25. Isolated from the blood cells were cultured with and without stimulation during 7 days. IL-7, IL-15 and anti-CD3 antibodies supplemented IL-2 were chosen as activators. Purifi ed Treg cells were labeled with CFSE dye to assess proliferation. We estimated that HP factors eff ectively maintain the number and phenotype (CD25+FoxP3+) of Treg in vitro. Also, in patients group we showed an increasing of CD4+CD25+FoxP3+ cells under all stimulation condition that may indicate the induction of Treg from conventional T cells. Herewith under IL-7 and IL-15 Treg cells from RA patients had a low proliferative activity than Treg from donors. The reduced proliferative activity of Treg in the group of RA-patients under IL-7 and IL-15 perhaps make a signifi - cant contribution to the development of the disease due to the delay of Treg pool reconstitution in the lymphopenia conditions on the initial stage. Furthermore, increased induction of CD4+CD25+FoxP3+ cells in PBMC cultures in patients group associated with pathogenesis of RA, since induced Treg have transient and unstable expression of FoxP3. 

作者简介

D. Shevyrev

Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology

编辑信件的主要联系方式.
Email: dr.daniil25@mail.ru

PhD student, laboratory of clinical immunopathology,

Novosibirsk

俄罗斯联邦

V. Kozlov

Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology

Email: fake@neicon.ru

Full Member of the Russian Academy of Sciences, doctor of medical sciences, professor,

Novosibirsk

俄罗斯联邦

V. Omelchenko

Research Institute of Clinical and Experimental Lymphology – a branch of the Institute of Cytology
and Genetics of the Siberian Branch of the Russian Academy of Sciences

Email: fake@neicon.ru

junior researcher, laboratory of connective tissue pathology,

Novosibirsk

俄罗斯联邦

参考

  1. Moxham V. F., Karegli J., Phillips R. E., Brown K. L., Tapmeier T. T., Hangartner R., Sacks S. H., Wong W. Homeostatic proliferation of lymphocytes results in augmented memory-like function and accelerated allograft rejection. J Immunol. 2008, Mar 15; 180(6):3910–8. DOI: https://doi.org/10.4049/jimmunol.180.6.3910.
  2. Duarte J. H., Zelenay S., Bergman M. L., Martins A. C., Demengeot J. Natural Treg cells spontaneously diff erentiate into pathogenic helper cells in lymphopenic conditions. Eur. J. Immunol. 2009, 39:948–955. doi: 10.1002/eji.200839196.
  3. Chinen T., Kannan A. K., Levine A. G., Fan X., Klein U., Zheng Y., Gasteiger G., Feng Y., Fontenot J. D., Rudensky A. Y. An essential role for the IL-2 receptor in Treg cell function. Nat Immunol. 2016 Nov; 17(11):1322– 1333. doi: 10.1038/ni.3540.
  4. Vang K. B., Yang J., Mahmud S. A., Burchill M. A., Vegoe A. L., Farrar M. A. Interleukin-2, -7 and -15, but not TSLP, Redundantly Govern CD4+Foxp3+ Regulatory T Cell Development. J Immunol. 2008 Sep 1; 181(5): 3285–3290.
  5. Komatsu N., Okamoto K., Sawa S., Nakashima T., Ohhora M., Kodama T., Tanaka S., Bluestone J. A., Takayanagi H. Pathogenic conversion of Foxp3+ T-cells into TH17 cells in autoimmune arthritis. Nat. Med. 2014, 20:62–70. doi: 10.1038/nm.3432.
  6. Zou T., Caton A. J. Dendritic Cells Induce Regulatory T Cell Proliferation through Antigen-Dependent and Independent Interactions. The Journal of Immunology. 2010, 185: 2790–2799. doi: 10.4049/jimmunol.0903740.

版权所有 © Shevyrev D.V., Kozlov V.A., Omelchenko V.O., 2019

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