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 naïve T cells into Th1 and Th2 effector subsets and the immunosuppressive activity of thymic-derived regulatory T cells. It is now clear that naïve 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 β and the transcription factor NFAT. Recent findings have begun to shed light on the mechanisms by which TGF-β and NFAT integrate multiple signaling inputs to determine the direction of naïve T-cell differentiation.