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Scientific article
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Control of central self-tolerance induction by autoreactive CD4+ thymocytes

Published inTrends in immunology, vol. 31, no. 2, p. 71-79
Publication date2010
Abstract

Medullary thymic epithelial cells (mTECs) are crucial for the selection of a T-cell-receptor (TCR) repertoire purged of self-reactive specificities, because these cells activate a promiscuous gene-expression program that leads to the synthesis of a wide array of peripheral tissue-restricted self-antigens. This review summarizes recent progress in our understanding of the cellular interactions, ligands, receptors and signal-transduction pathways that control mature-mTEC development. The particular focus is on new findings supporting the model that mature-mTEC development in the postnatal thymus depends on nuclear factor-kappaB (NF-kappaB) signaling induced by CD40-CD40 ligand, and receptor-activator-of-NF-kappaB (RANK)-RANK ligand interactions, and that these signals are delivered in the context of antigen-specific interactions between CD4(+) thymocytes carrying autoreactive TCRs and mTECs displaying cognate autoantigen-MHC-class-II complexes.

Keywords
  • Animals
  • Antigens, CD4/immunology
  • Autoimmunity
  • Epithelial Cells/cytology/immunology/metabolism
  • Humans
  • Receptors, Antigen, T-Cell/immunology
  • Self Tolerance
  • Signal Transduction
  • Thymus Gland/cytology/ immunology/metabolism
Citation (ISO format)
IRLA, Magali, HOLLANDER, Georg, REITH, Walter. Control of central self-tolerance induction by autoreactive CD4+ thymocytes. In: Trends in immunology, 2010, vol. 31, n° 2, p. 71–79. doi: 10.1016/j.it.2009.11.002
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ISSN of the journal1471-4906
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