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Immune Suppressive Activity and Lack of T Helper Differentiation Are Differentially Regulated in Natural Regulatory T Cells¹

Wei-ping Zeng^2,*,, Chawnshang Chang and Jiann-jyh Lai

^* Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, and Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642

The mechanism for controlling Th cytokine expression in natural regulatory T (nTreg) cells is unclear. Here, it was found that under polarizing conditions Foxp3 did not affect Th1 cell, partially inhibited Th17 cell, but greatly inhibited Th2 cell differentiation of conventional CD4 T cells. Under the polarizing conditions, nTreg cells failed to differentiate into Th2 and Th17 cells, but differentiated into IFN--producing cells. Such Foxp3-transduced CD4 T cells and nTreg cells expressed T-bet, GATA-3, or retinoic acid-related orphan receptor (ROR)t, and retroviral GATA-3 and RORt could not induce Th2 and Th17 differentiation from nTreg cells. However, regardless of their cytokine profiles, the Foxp3-transduced CD4 T cells and nTreg cells remained immune suppressive. These results suggested that it is possible to convert pathogenic Th cells to Treg-like cells for therapeutic application. In conclusion, our studies show that Foxp3 is sufficient for immune suppression, whereas the inhibition of cytokine expression requires additional mechanisms.

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 study is supported by a Senior Research Award from the Crohn’s and Colitis Foundation of America to W.Z.

² Address correspondence and reprint requests to Dr. Wei-ping Zeng, Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine, Marshall University, 1 John Marshall Drive, Huntington, WV 25701. E-mail address: zongb1{at}excite.com

³ Abbreviations used in this paper: nTreg cell, natural regulatory T cell; IBD, inflammatory bowel disease; MFI, mean fluorescence intensity; ROR, retinoic acid-related orphan receptor.

⁴ The online version of this article contains supplemental material.