Transcriptional Regulation of T Cell Tolerance

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

Research output: Chapter in Book/Report/Conference proceedingChapter


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
Number of pages20
ISBN (Print)9780470758618
Publication statusPublished - Apr 29 2009



  • 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.