Regulatory T cells and their role in etiology of selected diseases
Article Sidebar
Main Article Content
Abstract
Regulatory T cells (Tregs) are a phenotypic diverse group of cells responsible for regulation of immune response and play a key role in developing immune tolerance through active suppression. So far, several subtypes of regulatory lymphocytes have been classified, the most important of them being CD4+CD25+, Th3, Tr1 lymphocytes and NK cells. The CD4+CD25+ regulatory T cells that suppress proliferation and the releasing of proinflammatory cytokines from effector cells and/or directly inhibit antigen presenting cells, represents the most studied immunoregulatory cell type. Other subsets of Tregs cells with a very similar mechanism of action are generated in periphery, there are Tr1 cells which predominantly produce IL-10 and Th3 cells which predominantly produce TGF-β. Experimental in vivo studies have demonstrated that the absence of regulatory T cells can leads to organ and non-organ-specific autoimmune diseases such as thyroiditis, gastritis, rheumatoid arthritis, systemic lupus erythematosus or allergic and neoplastic diseases to occur, whereas the addition of this cell population can prevent or delay these diseases. Full understanding of physiology of these cells will be helpful in explaining mechanisms important in controlling the immune system activity, and the immunologic or pharmacologic modification of their function may be useful in the future as a new approach to immunotherapy.
Downloads
Article Details
Copyright: © Medical Education sp. z o.o. This is an Open Access article distributed under the terms of the Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). License (https://creativecommons.org/licenses/by-nc/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Address reprint requests to: Medical Education, Marcin Kuźma (marcin.kuzma@mededu.pl)
References
2. Seddiki N., Santner-Nanan B., Martinson J. et al.: Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J. Exp. Med. 2006, 7: 1693-700.
3. Yamaguchi T., Hirota K., Nagahama K. et al.: Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor. Immunity 2007, 1: 145-59.
4. Shevach E.M., DiPaolo R.A., Andersson J. et al.: The lifestyle of naturally occurring CD4+ CD25+ Foxp3+ regulatory T cells. Immunol. Rev. 2006, 212: 60-73.
5. Ebinuma H., Nakamoto N., Price Li Y. et al.: Identification and in-vitro expansion of functional antigen-specific CD25+Foxp3+ regulatory T-cells in hepatitis C virus infection. J. Virol. 2008, 82: 5043-5053.
6. Gavin M.A., Rasmussen J.P., Fontenot J.D. et al.: Foxp3-dependent programme of regulatory T-cell differentiation. Nature 2007, 7129: 771-5.
7. Roncarolo M.G., Gregori S., Battaglia M. et al.: Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunol. Rev. 2006, 212: 28-50.
8. Pillai V., Ortega S.B., Wang C.K.: Transient regulatory T-cells: a state attained by all activated human T-cells. Clin. Immunol. 2007, 123: 18-29.
9. Wang J., Ioan-Facsinay A., van der Voort E.I.: Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells. Eur. J. Immunol. 2007, 37: 129-38.
10. Zheng S.G., Wang J., Wang P. et al.: IL-2 is essential for TGF-β to convert naive CD4+CD25− cells to CD25+FOXP3+ regulatory T cells and for expansion of these cells. J. Immunol. 2007, 178: 2018-27.
11. Tran D.Q., Ramsey H., Shevach E.M.: Induction of FOXP3 expression in naive human CD4+FOXP3− T cells by T cell receptor stimulation is TGFβ-dependent but does not confer a regulatory phenotype. Blood 2007, 1: 463-4.
12. Tang Q., Henriksen K.J., Boden E.K. et al.: CD28 controls peripheral homeostasis of CD4+CD25+ regulatory T cells. J. Immunol. 2003, 171: 3348-3352.
13. Veldhoen M., Moncrieffe H., Hocking R.J. et al.: Modulation of dendritic cell function by naive and regulatory CD4+ T cells. J. Immunol. 2006, 176: 6202-6210.
14. Houot R., Perrot I., Garcia E. et al.: Human CD4+CD25high regulatory T cells modulate myeloid but not plasmacytoid dendritic cells activation. J. Immunol. 2006, 176: 5293-98.
15. Bopp T., Becker C., Klein M. et al.: Cyclic adenosine monophosphate is a key component of regulatory T cell mediated suppression. J. Exp. Med. 2007, 6: 1303-10.
16. Bluestone J.A., Abbas A.K.: Natural versus adaptive regulatory T cells. Nat. Rev. Immunol. 2003, 3: 253-57.
17. Kryczek I., Wei S., Zou L. et al.: Induction of B7-H4 on APCs through IL-10: novel suppressive mode for regulatory T cells. J. Immunol. 2006, 177: 40-44.
18. Berthelot J.M., Maugars Y.: Role for suppressor T cells in the pathogenesis of autoimmune diseases (including rheumatoid arthritis). Facts and hypotheses. Jt. Bone Spine 2004, 5: 374-80.
19. Levings M.K., Sangregorio R., Galbiati F. et al.: IFN-alpha and IL-10 induce the differentiationof human type 1 T regulatory cells. J. Immunol. 2001, 9: 5530-9.
20. Barrat F.J., Cua D.J., Boonstra A. et al.: In vitro generation of interleukin 10-producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1) – and Th2-inducing cytokines. J. Exp. Med. 2002, 195: 603-16.
21. Gregori S., Mangia P., Bacchetta R. et al.: An anti-CD45RO/RB monoclonal antibody modulates T cell responses via induction of apoptosis and generation of regulatory T cells. J. Exp. Med. 2005, 201: 1293-305.
22. Wakkach A., Cottrez F., Groux H.: Differentiation of regulatory T cells 1 is induced by CD2 costimulation. J. Immunol. 2001, 167: 3107-13.
23. Battaglia M., Stabilini A., Draghici E. et al.: Rapamycin and interleukin-10 treatment induces T regulatory type 1 cells that mediate antigenspecific transplantation tolerance. Diabetes 2006, 1: 40-9.
24. Annacker O., Asseman C., Read S.: Interleukin-10 in the regulation of T cell-induced colitis. J. Autoimmun. 2003, 4: 277-9.
25. Joetham A., Takeda K., Taube C. et al.: Naturally occurring lung CD4(+)CD25(+) T cell regulation of airway allergic responses depends on IL-10 induction of TGF-beta. J. Immunol. 2007, 3: 1433-42.
26. Knoechel B., Lohr J., Kahn E. et al.: Sequential development of interleukin 2-dependent eff ector and regulatory T cells in response to endogenous systemic antigen. J. Exp. Med. 2005, 202: 1375-86.
27. Stronge V.S., Salio M., Jones E.Y. et al.: A closer look at CD1d molecules: new horizons in studying NKT cells. Trends Immunol. 2007, 28: 455-62.
28. Zigmond E., Preston S., Pappo O. et al.: Betaglucosylceramide: a novel method for enhancement of natural killer T lymphocycte plasticity in murine models of immune-mediated disorders. Gut 2007, 56: 82-9.
29. Alvarado-Sánchez B., Hernández-Castro B., Portales-Pérez D. et al.: Regulatory T cells in patients with systemic lupus erythematosus. J. Autoimmun. 2006, 2: 110-8.
30. Behrens F., Himsel A., Rehart S. et al.: Imbalance in distribution of functional autologous regulatory T cells in rheumatoid arthritis. Ann. Rheum. Dis. 2007, 9: 1151-6.
31. Boissier M.C., Assier E., Biton J. et al.: Regulatory T cells (Treg) in rheumatoid arthritis. Joint Bone Spine 2009, 76: 10-14.
32. Winkler B., Hufnagl K., Spittler A. et al.: The role of Foxp3+ T cells in long-term efficacy of prophylactic and therapeutic mucosal tolerance induction in mice. Allergy 2006, 2: 173-80.
33. Taams L.S., Palmer D.B., Akbar A.N. et al.: Regulatory T cells in human disease and their potential for therapeutic manipulation. Immunology 2006, 1: 1-9.
34. Karagiannidis C., Akdis M., Holopainen P. et al.: Glucocorticoids upregulate Foxp3 expression and regulatory T cells in asthma. J. Allergy Clin. Immunol. 2004, 6: 1425-33.