New twists of T cell fate:: control of T cell activation and tolerance by TGF-β and NFAT

Protective and pathogenic immune responses were initially thought to be determined by the differentiation of naive T cells into Th1 and Th2 effector subsets and the immunosuppressive activity of thymic-derived regulatory T cells. It is now clear that naive T cells can also differentiate into 'induced' regulatory T cells or inflammatory T cells that secrete IL-17. These divergent T-cell subsets have opposing functions in imparting inflammation or tolerance, yet both developmental programs are controlled by the pluripotent cytokine transforming growth factor beta and the transcription factor NFAT. Recent findings have begun to shed light on the mechanisms by which TGF-beta and NFAT integrate multiple signaling inputs to determine the direction of naive T-cell differentiation.