Transcriptional Regulation of T Cell Tolerance

Brian T. Abe, Ayana Jordan, Vanessa M. Hubbard, Fernando Macian

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Self-reactive T cells that escape negative selection in the thymus must be kept under control in the periphery. Intrinsic functional inactivation and mechanisms of dominant tolerance mediated by regulatory T cells exist to keep self-reactive T cells in check. Both systems are regulated by the activation of specific programmes of gene expression. Suboptimal stimulation of T cells results in the activation of a calcium-/nuclear factor of activated T cells (NFAT)-dependent cell-intrinsic programme of inactivation that, among other consequences, induces epigenetic changes in the interleukin (IL)-2 promoter that silence IL-2 expression and make T cells hypo-responsive to subsequent stimulation. Foxp3 directs the expression of set of genes that specify regulatory T cell development. In regulatory T cells, Foxp3 mediates activation and suppression of transcription of target genes by recruiting a multi-subunit complex involved in histone modification and chromatin remodelling.

Original languageEnglish (US)
Title of host publicationThe Epigenetics of Autoimmune Diseases
PublisherJohn Wiley and Sons
Pages1-20
Number of pages20
ISBN (Print)9780470758618
DOIs
Publication statusPublished - Apr 29 2009

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Keywords

  • Gene related to anergy in lymphocytes (GRAIL)
  • Intercellular cell-adhesion molecule 1 (ICAM-1)
  • Lymphocyte function-associated antigen-1 (LFA-1)
  • Regulatory T cells (Tregs)
  • T cell anergy, referring to cell-intrinsic mechanism
  • T cell precursors
  • T cell receptors (TCRs)
  • Transcriptional regulation of T cell tolerance
  • Treg cell-specific programme of gene expression

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Abe, B. T., Jordan, A., Hubbard, V. M., & Macian, F. (2009). Transcriptional Regulation of T Cell Tolerance. In The Epigenetics of Autoimmune Diseases (pp. 1-20). John Wiley and Sons. https://doi.org/10.1002/9780470743553.ch1