A central role for central tolerance.

Abstract:

:Recent elucidation of the role of central tolerance in preventing organ-specific autoimmunity has changed our concepts of self/nonself discrimination. This paradigmatic shift is largely attributable to the discovery of promiscuous expression of tissue-restricted self-antigens (TRAs) by medullary thymic epithelial cells (mTECs). TRA expression in mTECs mirrors virtually all tissues of the body, irrespective of developmental or spatio-temporal expression patterns. This review summarizes current knowledge on the cellular and molecular regulation of TRA expression in mTECs, outlines relevant mechanisms of antigen presentation and modes of tolerance induction, and discusses implications for the pathogenesis of autoimmune diseases and other biological processes such as fertility, pregnancy, puberty, and tumor defense.

journal_name

Annu Rev Immunol

authors

Kyewski B,Klein L

doi

10.1146/annurev.immunol.23.021704.115601

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

571-606

eissn

0732-0582

issn

1545-3278

journal_volume

24

pub_type

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