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CUTTING EDGE |
-Mediated Induction of Foxp3+ T Regulatory CellsCellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
TGF-
is a pluripotent cytokine that is capable of inducing the expression of Foxp3 in naive T lymphocytes. TGF--induced cells are phenotypically similar to thymic-derived regulatory T cells in that they are anergic and suppressive. We have examined the cytokine and costimulatory molecule requirements for TGF--mediated induction and maintenance of Foxp3 by CD4+Foxp3– cells. IL-2 plays a non-redundant role in TGF--induced Foxp3 expression. Other common 
-chain-utilizing cytokines were unable to induce Foxp3 expression in IL-2-deficient T cells. The role of CD28 in the induction of Foxp3 was solely related to its capacity to enhance the endogenous production of IL-2. Foxp3 expression was stable in vitro and in vivo in the absence of IL-2. As TGF--induced T regulatory cells can be easily grown in vitro, they may prove useful for the treatment of autoimmune diseases, for the prevention of graft rejection, and graft versus host disease.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 Address correspondence and reprint requests to Dr. Ethan M. Shevach, National Institutes of Health, Laboratory of Immunology, Section of Cellular Immunology, Building 10, 11N315, Bethesda, MD 20892-1892. E-mail address: eshevach{at}niaid.nih.gov
2 Abbreviations used in this paper: Treg, regulatory T cell; nTreg, naturally occurring Treg; BMDC, bone marrow-derived dendritic cell.
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