TGF-βMERUPAKAN MEDIATOR IMUNOSUPRESI DARI SEL T CD4 + CD25 + IN VITRO
DOI:
https://doi.org/10.21776/ub.jkb.2007.023.03.5Abstract
Naturally the existency of regulatory T cells are represented by CD4+CD25+T cells. Those cells have been identified as a population of immuno-regulatory T cells, which mediated suppression of CD4+CD25+T cells by cell–cell contact. In the effectors phase the function of CD4+CD25+T regulatory T cells through the involvement of certain suppressive cytokines, such as TGF-β. In this study, we demonstrated that CD4+CD25+ cells produced high levels of Transforming Growth Factor-β (TGF-β) compared with CD4+CD25-T cells when stimulated by plate-bound anti-CD3 andsoluble anti-CD28. We observed that suppression ability of those cells could be abolished by the presence of anti–TGF-β. Finally, we found that stimulated CD4+CD25+T cells but not CD4+CD25-T cells express high and persistent levels of TGF-β. This finding strongly suggests that CD4+CD25+T cells exert immuno-suppression by cell–cell surfaces interaction involved cell of TGF-β. Keyword: Sel T CD4+CD25+, TGF-β, immunosupresionDownloads
References
Sakaguchi, S. Regulatory T cells: key controllers of immunologic self-tolerance. Cell.2000;101:455–458.
Powrie, F., M.W. Leach, S.Mauze, L.B. Caddle, and R.L.Coffman. Phenotypically distinct subsets of CD4+T cells induce or protect from chronic intestinal inflammation in C. B-17 SCID mice. Int. Immunol. 2000; 5:1461–1471.
Read, S., V. Malmstrom, and F. Powrie.. Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25+CD4+ regulatory cells that control intestinal inflammation. J. Exp. Med.2000;192:295–302.
Asseman, C., S. Mauze, M.W. Leach, R.L. Coffman, and F.Powrie. An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J. Exp. Med. 2001;190:995–1004.
Neurath, M.F., I. Fuss, B.L. Kelsall, D.H. Presky, W.Waegell, and W. Strober.. Experimental granulomatous colitis in mice is abrogated by induction of TGF-beta–mediated oral tolerance. J. Exp. Med.1999;183:2605–2616.
Groux, H., A. O’Garra, M. Bigler, M. Rouleau, S. Antonenko, J.E. de Vries, and M.G. Roncarolo. CD4 T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature.1997;389:737–742.
Takahashi, T., Y. Kuniyasu, M. Toda, N. Sakaguchi, M.Itoh, M. Iwata, J. Shimizu, and S. Sakaguchi.. Immunologic self-tolerance maintained by CD4+CD25+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Int. Immunol.1998;10:1969–1980.
Thornton, A.M., and E.M. Shevach. 1998. CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J. Exp.Med.1998;188:287–296.
Kitani, A., I.J. Fuss, K. Nakamura, O.M. Schwartz, T.Usui, and W. Strober. Treatment of experimental (trinitrobenzene sulfonic acid) colitis by intranasal administrationof transforming growth factor (TGF)-beta1 plasmid:TGFbeta1 mediated suppression of T helper cell type 1 response occurs by interleukin (IL)-10 induction and IL-12 receptorbeta2 chain down regulation. J. Exp. Med.2000;192:41–52.
Takahashi, T., T. Tagami, S. Yamazaki, T. Uede, J. Shimizu, N. Sakaguchi, T.W. Mak, and S. Sakaguchi. Immuno-Shevach EM: Certified professionals: CD4+CD25+ suppressor T cells. J Exp Med 2001, 193:41-46.
Asano M, Toda M, Sakaguchi N and Sakaguchi S. Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation.J. Exp. Med. 1996. 184: 387-396.
Jonuleit H, Schmitt E, Stassen M, Tuettenberg A, Knop J, Enk AH. Identification and functional characterization of human CD4+CD25+ T cells with regulatory properties isolated from peripheral blood. J Exp Med 2001, 193:1285-1294.
Kuniyasu Y, Takahashi T, Itoh M, Shimizu J, Toda G, Sakaguchi S: Naturally anergic and suppressive CD25+CD4+ T cells as a functionally and phenotypically distinctimmunoregulatory T cell subpopulation. Int Immunol 2000, 12:1145-1155.
Shevach EM: Regulatory T cells in autoimmmunity. Annu Rev Immunol 2000, 18:423-449.
Yamagiwa S, Gray JD, Hashimoto S, Horwitz DA: A role for TGF-beta in the generation and expansion of CD4+CD25+ regulatory T cells from human peripheral blood. J Immunol2001, 166:7282-7289.
Levings MK, Sangregorio R, Roncarolo MG: Human CD4+CD25+ T regulatory cells suppress naive and memory T cell proliferation and can be expanded in vitro without loss of function. J Exp Med 2001, 193:1295-1302.
Alegre, M.L., P.J. Noel, B.J. Eisfelder, E. Chuang,M.R. Clark, S.L. Reiner, and C.B. Thompson. Regulation of surface and intracellular expression of CTLA-4 on mouse T cells. J. Immunol.1996;157:4762–4770.
Piccirillo CA, Shevach EM: Cutting edge: control of CD8+ T cell activation by CD4+CD25+ immunoregulatory cells. J Immunol2001, 167:1137-1140.
Annacker, O., R. Pimenta-Araujo, O. Burlen-Defranoux,T.C. Barbosa, A. Cumano, and A. Bandeira. CD4+CD25+ T cells regulate the expansion of peripheral CD4 T cells through the production of IL-10. J. Immunol.2001;166:3008–3018.
Krummel, M.F., and J.P. Allison. CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells. J. Exp. Med. 1996;183:2533–2540.
Thornton, A.M., and E.M. Shevach. Suppressor effector function of CD4+CD25+ immuno-regulatory T cells is antigen non specific. J. Immunol. 2000;164:183–190.
Kuniyasu, Y., T. Takahashi, M. Itoh, J. Shimizu, G. Toda and S. Sakaguchi. Naturally anergic and suppressive CD4+CD25+ T cells as a functionally and phenotypically distinct immuno-regulatory T cell sub population. Int. Immunol.2000;12:1145–1155.
Salomon, B., D.J. Lenschow, L. Rhee, N. Ashourian, B.Singh, A. Sharpe, and J.A. Bluestone. 2000. B7/CD28 co-stimulation is essential for the homeostasis of theCD4+CD25+ immuno-regulatory T cells that control autoimmune diabetes. Immunity.2000;12:431–440.
Chen, W., W. Jin, and S.M. Wahl. Engagement of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) induces transforming growth factor beta (TGF-beta) production by murine CD4+ T cells. J. Exp. Med. 1998;188:1849–1857.
Sakaguchi S, Fukuma K, Kuribayashi K, Masuda T: Organ-specific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cells in natural self-tolerance; deficitof a T cell subset as a possible cause of autoimmune disease. J Exp Med 1999, 161:72-87.
Marcelletti, J.F., and D.H. Katz. IL-10 stimulates murine antigen-driven antibody responses in vitro by regulating helper cell subset participation. Cell Immunol.1996;167:86–98.
Crawford, S.E., V. Stellmach, J.E. Murphy-Ullrich, S.M. Ribeiro, J. Lawler, R.O. Hynes, G.P. Boivin, and N. Bouck. Thrombospondin-1 is a major activator of TGF-beta1 in vivo. Cell.1998; 93:1159–1170.
Papiernik, M., M.L. de Moraes, C. Pontoux, F. Vasseur, and C. Penit. Regulatory CD4 T cells: expression of IL-2R alpha chain, resistance to clonal deletion and IL-2 dependency. Int. Immunol.1998; 10:371–378.
Downloads
Published
Issue
Section
License
Authors who publish with this journal agree to the following terms:- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).