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- and Antigen-Driven Conversion of Naive CD4 T Cells into CD25+Foxp3+ T cells1Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037
Naive CD4 T cells can develop into regulatory T cells by acquiring the transcription factor Foxp3. Combined signals from the TCR, CD28, IL-2R, and TGF-
R promote Foxp3 expression in activated naive CD25– CD4 T cells. Here we show that OX40 (CD134) signaling inhibits TGF--driven Foxp3 mRNA and suppresses the conversion of naive Ag-specific transgenic CD4 T cells into CD25+Foxp3+ T cells. These data identify OX40 as a negative regulator of Foxp3 and suggest that OX40 can concomitantly promote effector T cell generation while antagonizing the differentiation of adaptive Foxp3+ regulatory T cells.
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 This work was supported by National Institutes of Health Grant CA91837 and AI070535 (to M.C.). This is manuscript no. 880 from the La Jolla Institute for Allergy and Immunology.
2 Address correspondence and reprint requests to Dr. Michael Croft, Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037. E-mail address: mick{at}liai.org
3 Abbreviations used in this paper: Treg, regulatory T cell; HPRT, hypoxanthine phosphoribosyltransferase; MCC, mouse cytochrome c.
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