Centre de Physiopathologie de Toulouse Purpan, Université Toulouse III Paul-Sabatier, Toulouse F-31300, France.
Curr Opin Immunol. 2012 Feb;24(1):99-104. doi: 10.1016/j.coi.2012.01.008. Epub 2012 Jan 30.
The stromal network of the thymus provides a unique environment that supports the development of mature CD4(+) and CD8(+) T cells expressing a very diverse repertoire of T cell receptors (TCR) with limited reactivity to self-antigens. Thymic cortical epithelial cells (cTECs) are specialized antigen-presenting cells (APCs) that promote the positive selection of developing thymocytes while medullary thymic epithelial cells (mTECs) and thymic dendritic cells (tDCs) induce central tolerance to self-antigens. Recent studies showed that cTECs express a unique set of proteases involved in the generation of self-peptides presented by major-histocompatibility encoded molecules (pMHC) and consequently may express a unique set of pMHC complexes. Conversely, the stromal cells of the medulla developed several mechanisms to mirror as closely as possible the constellation of self-peptides derived from peripheral tissues. Here, we discuss how these different features allow for the development of a highly diverse but poorly self-reactive repertoire of functional T cells.
胸腺的基质网络提供了一个独特的环境，支持成熟的 CD4(+)和 CD8(+)T 细胞的发育，这些细胞表达的 T 细胞受体 (TCR) 具有非常多样化的 repertoire，对自身抗原的反应性有限。胸腺皮质上皮细胞 (cTECs) 是专门的抗原呈递细胞 (APCs)，它们促进发育中的胸腺细胞的阳性选择，而髓质胸腺上皮细胞 (mTECs) 和胸腺树突状细胞 (tDCs) 诱导对自身抗原的中枢耐受。最近的研究表明，cTECs 表达了一组独特的蛋白酶，这些蛋白酶参与了主要组织相容性编码分子 (pMHC) 呈现的自身肽的产生，因此可能表达一组独特的 pMHC 复合物。相反，髓质的基质细胞发展了几种机制，尽可能地模拟来自外周组织的自身肽的组合。在这里，我们讨论了这些不同的特征如何允许发育出高度多样化但对自身反应性差的功能性 T 细胞 repertoire。
