Regulation of T-cell tolerance by calcium/NFAT signaling.
Cells that escape negative selection in the thymus must be inactivated or eliminated in the periphery through a series of mechanisms that include the induction of anergy, dominant suppression by regulatory T cells, and peripheral deletion of self-reactive T cells. Calcium signaling plays a central role in the induction of anergy in T cells, which become functionally inactivated and incapable of proliferating and expressing cytokines following antigen re-encounter. Suboptimal stimulation of T cells results in the activation of a calcium/calcineurin/nuclear factor of activated T cells-dependent cell-intrinsic program of self-inactivation. The proteins encoded by those genes are required to impose a state of functional unresponsiveness through different mechanisms that include downregulation of T-cell receptor signaling and inhibition of cytokine transcription.
Baine
Ian
I
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Abe
Brian T
BT
Macian
Fernando
F
D000818:Animals; D020013:Calcium Signaling; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007108:Immune Tolerance; D050778:NFATC Transcription Factors / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
D016207:Cytokines; D050778:NFATC Transcription Factors; D011948:Receptors, Antigen, T-Cell