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-β

Recent studies have shown that TGF-β 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-β, 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-β 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-β). 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.