Mechanisms of self-inactivation in anergic T cells

Self-reactive T cells that escape negative selection in the thymus must be inactivated or eliminated in the periphery. In response to a partial or suboptimal stimulation, T cells become anergic and unable to proliferate and express cytokines in response subsequent re-encounters with antigen. Calcium signaling plays a central role in the induction of anergy, causing the activation of a calcium/calcineurin/NFAT-dependent cell-intrinsic program of self-inactivation. This review will focus on our current knowledge on the mechanisms that regulate the expression of an anergy-specific program of gene expression in T cells, and how the proteins encoded by those genes impose a state of functional unresponsiveness by targeting and modulating the activity of crucial events required for the activation of T cells, which include downregulation of TCR signaling and inhibition of cytokine transcription.