Control of central self-tolerance induction by autoreactive CD4+ thymocytes.
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.
Irla
Magali
M
University of Geneva, Faculty of Medicine, CMU, 1 rue Michel-Servet, CH-1211, Geneva, Switzerland.
Hollander
Georg
G
Reith
Walter
W
D000818:Animals; D015551:Autoimmunity; D015704:CD4 Antigens / Q000276:immunology; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D017634:Self Tolerance; D015398:Signal Transduction; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D015704:CD4 Antigens; D011948:Receptors, Antigen, T-Cell