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

Regulation of T-cell tolerance by calcium/NFAT signaling.

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Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.


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.

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