New twists of T cell fate: control of T cell activation and tolerance by TGF-beta 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 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 naïve T-cell differentiation.
Sundrud
Mark S
MS
Department of Pathology, Harvard Medical School, and The CBR Institute for Biomedical Research Inc, Boston, MA 02115, USA.
Rao
Anjana
A
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation / Q000276:immunology*; D050778:NFATC Transcription Factors / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D050778:NFATC Transcription Factors; D016212:Transforming Growth Factor beta