The cellular mechanism of Aire control of T cell tolerance

Mark S. Anderson, Emily S. Venanzi, Zhibin Chen, Stuart P. Berzins, Christophe Benoist, Diane Mathis

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441 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)227-239
Number of pages13
JournalImmunity
Volume23
Issue number2
DOIs
StatePublished - Aug 1 2005

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Anderson, M. S., Venanzi, E. S., Chen, Z., Berzins, S. P., Benoist, C., & Mathis, D. (2005). The cellular mechanism of Aire control of T cell tolerance. Immunity, 23(2), 227-239. https://doi.org/10.1016/j.immuni.2005.07.005