TGF-beta indirectly favours the development of human Th17 cells by inhibiting Th1 cells.

Abstract Human Th17 clones and circulating Th17 cells showed lower susceptibility to the antiproliferative effect of TGF-b than Th1 and Th2 clones or circulating Th1-oriented T cells, respectively. Accordingly, human Th17 cells exhibited lower expression of clusterin, and higher Bcl-2 expression and reduced apoptosis in the presence of TGF-b, in comparison with Th1 cells. Umbilical cord blood naı¨ve CD161+CD4+ T cells, which contain the precursors of human Th17 cells, differentiated into IL-17A-producing cells only in response to IL-1b plus IL-23, even in serum-free cultures. TGF-b had no effect on constitutive RORgt expression by umbilical cord blood CD161+ T cells but it increased the relative proportions of CD161+ T cells differentiating into Th17 cells in response to IL-1b plus IL-23, whereas under the same conditions it inhibited both T-bet expression and Th1 development. These data suggest that TGF-b is not critical for the differentiation of human Th17 cells, but indirectly favors their expansion because Th17 cells are poorly susceptible to its suppressive effects.