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Control of central self-tolerance induction by autoreactive CD4+ thymocytes
|Published in||Trends in Immunology. 2010, vol. 31, no. 2, p. 71-79|
|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|
|Research group||Groupe Reith Walter (pathologie et immunologie) (282)|