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Cutting Edge: Regulatory T Cells Induce CD4⁺CD25^–Foxp3^– T Cells or Are Self-Induced to Become Th17 Cells in the Absence of Exogenous TGF-

Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892

Recent studies have shown that TGF- together with IL-6 induce the differentiation of IL-17-producing T cells (Th17) T cells. We therefore examined whether CD4⁺CD25⁺Foxp3⁺ regulatory T cells, i.e., cells previously shown to produce TGF-, serve as Th17 inducers. We found that upon activation purified CD25⁺ T cells (or sorted GFP⁺ T cells obtained from Foxp3-GFP knockin mice) produce high amounts of soluble TGF- and when cultured with CD4⁺CD25^–Foxp3^– T cells in the presence of IL-6 induce the latter to differentiate into Th17 cells. Perhaps more importantly, upon activation, CD4⁺CD25⁺Foxp3⁺(GFP⁺) T cells themselves differentiate into Th17 cells in the presence of IL-6 (and in the absence of exogenous TGF-). These results indicate that CD4⁺CD25⁺Foxp3⁺ regulatory T cells can function as inducers of Th17 cells and can differentiate into Th17 cells. They thus have important implications to our understanding of regulatory T cell function and their possible therapeutic use.

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¹ Address correspondence and reprint requests to Dr. Warren Strober, Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Clinical Research Center, Room 5W3940, 10 Center Drive, Bethesda, MD 20892. E-mail: wstrober{at}niaid.nih.gov

² Abbreviations used in this paper: Treg, regulatory T cell; Th17, IL-17- producing cells; DC, dendritic cell.

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