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-ant...
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| Veröffentlicht in: | Trends in immunology 2010-02, Vol.31 (2), p.71-79 |
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| creator | Irla, Magali Hollander, Georg Reith, Walter |
| description | 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-κB (NF-κB) signaling induced by CD40–CD40 ligand, and receptor-activator-of-NF-κB (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. |
| doi_str_mv | 10.1016/j.it.2009.11.002 |
| format | Article |
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| ispartof | Trends in immunology, 2010-02, Vol.31 (2), p.71-79 |
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| subjects | Allergy and Immunology Animals Autoimmunity CD4 Antigens - immunology Defects Epithelial Cells - cytology Epithelial Cells - immunology Epithelial Cells - metabolism Gene expression Humans Kinases Population Receptors, Antigen, T-Cell - immunology Rodents Self Tolerance Signal Transduction Thymus Gland - cytology Thymus Gland - immunology Thymus Gland - metabolism |
| title | Control of central self-tolerance induction by autoreactive CD4+ thymocytes |
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