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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.
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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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