Foxp3-independent mechanism by which TGF-β controls peripheral T cell tolerance

Significance A functional immune system requires a highly diverse repertoire of T cells to optimize protection against foreign pathogens while maintaining tolerance against self-antigens. Two critical pathways in the control of T cell tolerance are the cytokine TGF-β and Foxp3-expressing Treg cells. However, since TGF-β promotes Treg cell development, and Treg cells also produce the cytokine, whether TGF-β and Treg cells are part of the same regulatory module to repress self-reactive T cells or function as distinct pathways remains incompletely understood. Using a mouse model of autoimmune diabetes, this study elucidates a dominant role for a Foxp3-independent mechanism of TGF-β signaling in the regulation of T cell tolerance.