The cellular mechanism of Aire control of T cell tolerance

Immunity. 2005 Aug;23(2):227-39. doi: 10.1016/j.immuni.2005.07.005.

Abstract

Aire promotes the tolerization of thymocytes by inducing the expression of a battery of peripheral-tissue antigens in thymic medullary epithelial cells. We demonstrate that the cellular mechanism by which Aire exerts its tolerance-promoting function is not primarily positive selection of regulatory T cells, but rather negative selection of T effector cells. Surprisingly, supplementing its influence on the transcription of genes encoding peripheral-tissue antigens, Aire somehow enhances the antigen-presentation capability of medullary epithelial cells. Thus, this transcriptional control element promotes central tolerance both by furnishing a specific thymic stromal cell type with a repertoire of self antigens and by better arming such cells to present these antigens to differentiating thymocytes. In Aire's absence, autoimmunity and ultimately overt autoimmune disease develops.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Clonal Deletion / genetics
  • Clonal Deletion / immunology
  • Immune Tolerance* / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Nude
  • Mice, Transgenic
  • Receptors, Interleukin-2 / immunology
  • Spleen / immunology
  • T-Lymphocyte Subsets / immunology*
  • Thymus Gland / immunology
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Transcription Factors / physiology*

Substances

  • APECED protein
  • Receptors, Interleukin-2
  • Transcription Factors