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CD4+CD25+ Regulatory T Cells Can Mediate Suppressor Function in the Absence of Transforming Growth Factor β1 Production and Responsiveness

CD4+CD25+ Regulatory T Cells Can Mediate Suppressor Function in the Absence of Transforming... CD4 + CD25 + regulatory T cells inhibit organ-specific autoimmune diseases induced by CD4 + CD25 − T cells and are potent suppressors of T cell activation in vitro. Their mechanism of suppression remains unknown, but most in vitro studies suggest that it is cell contact–dependent and cytokine independent. The role of TGF-β1 in CD4 + CD25 + suppressor function remains unclear. While most studies have failed to reverse suppression with anti–transforming growth factor (TGF)-β1 in vitro, one recent study has reported that CD4 + CD25 + T cells express cell surface TGF-β1 and that suppression can be completely abrogated by high concentrations of anti–TGF-β suggesting that cell-associated TGF-β1 was the primary effector of CD4 + CD25 + -mediated suppression. Here, we have reevaluated the role of TGF-β1 in CD4 + CD25 + -mediated suppression. Neutralization of TGF-β1 with either monoclonal antibody (mAb) or soluble TGF-βRII-Fc did not reverse in vitro suppression mediated by resting or activated CD4 + CD25 + T cells. Responder T cells from Smad3 −/− or dominant-negative TGF-β type RII transgenic (DNRIITg) mice, that are both unresponsive to TGF-β1–induced growth arrest, were as susceptible to CD4 + CD25 + -mediated suppression as T cells from wild-type mice. Furthermore, CD4 + CD25 + T cells from neonatal TGF-β1 −/− mice were as suppressive as CD4 + CD25 + from TGF-β1 +/+ mice. Collectively, these results demonstrate that CD4 + CD25 + suppressor function can occur independently of TGF-β1. CD4 + suppressor T cells autoimmunity tolerance immunoregulation IL-2 receptor Footnotes ↵ * Abbreviations used in this paper: AIG, autoimmune gastritis; DNRIITg, dominant-negative TGF-β type RII transgenic; IBD, inflammatory bowel disease; WT, wild-type. Submitted: 15 April 2002 Accepted: 5 June 2002 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Experimental Medicine Rockefeller University Press

CD4+CD25+ Regulatory T Cells Can Mediate Suppressor Function in the Absence of Transforming Growth Factor β1 Production and Responsiveness

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Publisher
Rockefeller University Press
Copyright
© 2002 Rockefeller University Press
ISSN
0022-1007
eISSN
1540-9538
DOI
10.1084/jem.20020590
Publisher site
See Article on Publisher Site

Abstract

CD4 + CD25 + regulatory T cells inhibit organ-specific autoimmune diseases induced by CD4 + CD25 − T cells and are potent suppressors of T cell activation in vitro. Their mechanism of suppression remains unknown, but most in vitro studies suggest that it is cell contact–dependent and cytokine independent. The role of TGF-β1 in CD4 + CD25 + suppressor function remains unclear. While most studies have failed to reverse suppression with anti–transforming growth factor (TGF)-β1 in vitro, one recent study has reported that CD4 + CD25 + T cells express cell surface TGF-β1 and that suppression can be completely abrogated by high concentrations of anti–TGF-β suggesting that cell-associated TGF-β1 was the primary effector of CD4 + CD25 + -mediated suppression. Here, we have reevaluated the role of TGF-β1 in CD4 + CD25 + -mediated suppression. Neutralization of TGF-β1 with either monoclonal antibody (mAb) or soluble TGF-βRII-Fc did not reverse in vitro suppression mediated by resting or activated CD4 + CD25 + T cells. Responder T cells from Smad3 −/− or dominant-negative TGF-β type RII transgenic (DNRIITg) mice, that are both unresponsive to TGF-β1–induced growth arrest, were as susceptible to CD4 + CD25 + -mediated suppression as T cells from wild-type mice. Furthermore, CD4 + CD25 + T cells from neonatal TGF-β1 −/− mice were as suppressive as CD4 + CD25 + from TGF-β1 +/+ mice. Collectively, these results demonstrate that CD4 + CD25 + suppressor function can occur independently of TGF-β1. CD4 + suppressor T cells autoimmunity tolerance immunoregulation IL-2 receptor Footnotes ↵ * Abbreviations used in this paper: AIG, autoimmune gastritis; DNRIITg, dominant-negative TGF-β type RII transgenic; IBD, inflammatory bowel disease; WT, wild-type. Submitted: 15 April 2002 Accepted: 5 June 2002

Journal

The Journal of Experimental Medicine – Rockefeller University Press

Published: Jul 15, 2002

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