Transcriptional regulation of T cell tolerance.
Self-reactive T cells that escape negative selection in the thymus must be kept under control in the periphery. Mechanisms of peripheral tolerance include deletion or functional inactivation of self-reactive T cells and mechanisms of dominant tolerance mediated by regulatory T cells. In the absence of costimulation, T cell receptor (TCR) engagement results in unopposed calcium signaling that leads to the activation of a cell-intrinsic program of inactivation, which makes T cells hyporesponsive to subsequent stimulations. The activation of this program in anergic T cells is a consequence of the induction of a nuclear factor of activated T cells (NFAT)-dependent program of gene expression. Recent studies have offered new insights into the mechanisms responsible for the implementation and maintenance of T cell anergy and have provided evidence that the proteins encoded by the genes upregulated in anergic T cells are responsible for the implementation of anergy by interfering with TCR signaling or directly inhibiting cytokine gene transcription.
Bandyopadhyay
Sanmay
S
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Soto-Nieves
Noemí
N
Macián
Fernando
F
D000818:Animals; D017635:Clonal Anergy; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic