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Cutting Edge: Antigen-Specific TGFβ-Induced Regulatory T Cells Suppress Th17-Mediated Autoimmune Disease¹

Eva N. Huter^2,*, Georg H. Stummvoll^2,, Richard J. DiPaolo, Deborah D. Glass^* and Ethan M. Shevach^3,*

^* Laboratory of Immunology, Cellular Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; Department of Rheumatology, Medical University of Vienna, Vienna, Austria; and Molecular Microbiology and Immunology, St. Louis University School of Medicine, St. Louis, MO 63104

CD4⁺ T cells from the TCR transgenic TxA23 mouse recognize a peptide from the H/K-ATPase -chain. When TxA23 CD4⁺ thymocytes are differentiated into Th1, Th2, and Th17 lines, all three subpopulations induced autoimmune gastritis (AIG) upon transfer into nu/nu recipients. The induction of AIG by naive T cells or by Th1 or Th2 cell lines could be prevented by the cotransfer of polyclonal Foxp3⁺ T regulatory cells (nTreg), whereas Th17-induced AIG was resistant to suppression. We compared the capacity of different types of Treg to suppress Th17-mediated AIG. Cotransfer of either nTreg or polyclonal TGFβ-induced Treg (iTreg) did not prevent AIG, while cotransfer of TGFβ-induced Ag-specific TxA23 iTreg completely prevented the development of disease. Ag-specific iTreg were able to suppress Th17-mediated disease when injected 6 days after the Th17 effectors. The implications of these results for the use of Treg for the cellular biotherapy of autoimmune disease are discussed.

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 the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases.

² E.N.H. and G.H.S. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Ethan M. Shevach, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Building 10, Room 11N315, National Institutes of Health, Bethesda, MD 20892. E-mail address: eshevach{at}niaid.nih.gov

⁴ Abbreviations used in this paper: AIG, autoimmune gastritis; gLN, gastric lymph node; Treg, regulatory T cell; iTreg, TGFβ-induced Treg; nTreg, thymic-derived Treg; WT, wild type.