Th17 cells generated in the absence of TGF-β induce experimental allergic encephalitis upon adoptive transfer.

The discovery of IL-17-producing helper T cells (Th17) has led to new concepts of T-cell differentiation and immunity. Importantly, Th17 cells are thought to be important drivers of autoimmunity. TGF-β and IL-6 in combination were shown to induce differentiation of murine naive CD4 T cells into IL-17-producing cells in vitro. By contrast, human Th17 differentiation was shown to be independent of TGF-β and could be induced by IL-6 in conjunction with IL-21 or with IL-1. Ghoreschi et al. have elegantly demonstrated that mouse Th17 cell differentiation can also occur in the absence of TGF-β. A combination of IL-23, IL-1 and IL-6 can give rise to IL-17-producing cells, which are characterized by the expression of T-bet. Intriguingly, the adoptive transfer of such in vitro differentiated Th17 cells into lymphocyte-deficient mice resulted in the induction of experimental allergic encephalitis, which was more severe than in mice receiving Th17 cells differentiated in the presence of TGF-β. Collectively, the results suggest that a subpopulation of Th17 cells differentiated in the absence of TGF-β, expressing T-bet and RORγt, occur in vivo and may be responsible for autoimmunity.