Transforming growth factor-β protein inversely regulates in vivo differentiation of interleukin-17 (IL-17)-producing CD4 ⁺ and CD8 ⁺ T cells

TGF-β is a pleiotropic cytokine that predominantly exerts inhibitory functions in the immune system. Unexpectedly, the in vitro differentiation of both Th17 and Tc17 cells requires TGF-β. However, animals that are impaired in TGF-β signaling (TGF-βRIIDN mice) display multiorgan autoimmune disorders. Here we show that CD4 ⁺ T cells from TGF-βRIIDN mice are resistant to Th17 cell differentiation and, paradoxically, that CD8 ⁺ T cells from these animals spontaneously acquire an IL-17-producing phenotype. Neutralization of IL-17 or depletion of CD8 ⁺ T cells dramatically inhibited inflammation in TGF-βRIIDN mice. Therefore, the absence of TGF-β triggers spontaneous differentiation of IL-17-producing CD8 ⁺ T cells, suggesting that the in vivo and in vitro conditions that promote the differentiation of IL-17-producing CD8 ⁺ T cells are distinct.