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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.
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 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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