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

Research output: Contribution to journalArticle

441 Citations (Scopus)

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

Fingerprint

Thymocytes
T-Lymphocytes
Antigens
Central Tolerance
Epithelial Cells
Autoantigens
Antigen Presentation
Regulatory T-Lymphocytes
Stromal Cells
Autoimmunity
Autoimmune Diseases
Genes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

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

The cellular mechanism of Aire control of T cell tolerance. / Anderson, Mark S.; Venanzi, Emily S.; Chen, Zhibin; Berzins, Stuart P.; Benoist, Christophe; Mathis, Diane.

In: Immunity, Vol. 23, No. 2, 01.08.2005, p. 227-239.

Research output: Contribution to journalArticle

Anderson, MS, Venanzi, ES, Chen, Z, Berzins, SP, Benoist, C & Mathis, D 2005, 'The cellular mechanism of Aire control of T cell tolerance', Immunity, vol. 23, no. 2, pp. 227-239. https://doi.org/10.1016/j.immuni.2005.07.005
Anderson MS, Venanzi ES, Chen Z, Berzins SP, Benoist C, Mathis D. The cellular mechanism of Aire control of T cell tolerance. Immunity. 2005 Aug 1;23(2):227-239. https://doi.org/10.1016/j.immuni.2005.07.005
Anderson, Mark S. ; Venanzi, Emily S. ; Chen, Zhibin ; Berzins, Stuart P. ; Benoist, Christophe ; Mathis, Diane. / The cellular mechanism of Aire control of T cell tolerance. In: Immunity. 2005 ; Vol. 23, No. 2. pp. 227-239.
@article{a0a19f9bedde4c3f9e08660f5d085ecd,
title = "The cellular mechanism of Aire control of T cell tolerance",
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.",
author = "Anderson, {Mark S.} and Venanzi, {Emily S.} and Zhibin Chen and Berzins, {Stuart P.} and Christophe Benoist and Diane Mathis",
year = "2005",
month = "8",
day = "1",
doi = "10.1016/j.immuni.2005.07.005",
language = "English",
volume = "23",
pages = "227--239",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - The cellular mechanism of Aire control of T cell tolerance

AU - Anderson, Mark S.

AU - Venanzi, Emily S.

AU - Chen, Zhibin

AU - Berzins, Stuart P.

AU - Benoist, Christophe

AU - Mathis, Diane

PY - 2005/8/1

Y1 - 2005/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=23844558032&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23844558032&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2005.07.005

DO - 10.1016/j.immuni.2005.07.005

M3 - Article

C2 - 16111640

AN - SCOPUS:23844558032

VL - 23

SP - 227

EP - 239

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 2

ER -