Regulation of T-cell tolerance by calcium/NFAT signaling

Immunol Rev. 2009 Sep;231(1):225-40. doi: 10.1111/j.1600-065X.2009.00817.x.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Calcium Signaling*
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Humans
  • Immune Tolerance*
  • NFATC Transcription Factors / metabolism*
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*


  • Cytokines
  • NFATC Transcription Factors
  • Receptors, Antigen, T-Cell