University of Geneva, Faculty of Medicine, CMU, 1 rue Michel-Servet, CH-1211, Geneva, Switzerland.
Trends Immunol. 2010 Feb;31(2):71-9. doi: 10.1016/j.it.2009.11.002. Epub 2009 Dec 7.
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.
髓质胸腺上皮细胞（mTEC）对于清除自身反应性特异性的 T 细胞受体（TCR）库的选择至关重要，因为这些细胞激活了一种混杂的基因表达程序，导致广泛的外周组织受限的自身抗原的合成。这篇综述总结了我们对控制成熟 mTEC 发育的细胞相互作用、配体、受体和信号转导途径的最新理解进展。特别关注的是支持以下模型的新发现：即出生后胸腺中成熟 mTEC 的发育依赖于 CD40-CD40 配体和受体激活剂 NF-κB（RANK）-RANK 配体相互作用诱导的核因子-κB（NF-κB）信号，并且这些信号是在携带自身反应性 TCR 的 CD4(+) 胸腺细胞与显示同源自身抗原-MHC 类 II 复合物的 mTEC 之间的抗原特异性相互作用的背景下传递的。
