Gallegos Alena M, Bevan Michael J
Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195-7370, USA.
Immunol Rev. 2006 Feb;209:290-6. doi: 10.1111/j.0105-2896.2006.00348.x.
T-cell development is a highly coordinated process that depends on interactions between thymocytes, thymic epithelium, and bone marrow (BM)-derived dendritic cells (DCs). Before entering the peripheral T-cell pool, thymocytes are subject to negative selection, a process that eliminates (or deletes) T cells with high affinity toward self-antigens and therefore promotes self-tolerance. These self-antigens include those that are broadly expressed ubiquitous antigens and those whose expression is restricted to a few tissues, tissue-specific antigens (TSAs). Expression of TSAs in the thymus is mostly a property of medullary thymic epithelial cells (mTECs), and because these cells may be less capable than BM-derived DCs at mediating negative selection to ubiquitous antigens, we investigated the roles of both of these cell types in tolerance to TSAs. Here, we review our studies in which we found that mTECs were competent mediators of negative selection to a subset of TSA-reactive T cells, while thymic DCs extend the range of TSA-reactive T cells that undergo negative selection by capturing TSAs from mTECs. In addition, we recently investigated the efficiency of central tolerance to TSA during ontogeny, and we report that this process was less efficient in neonates than adult animals.
T细胞发育是一个高度协调的过程，它依赖于胸腺细胞、胸腺上皮细胞和骨髓（BM）来源的树突状细胞（DC）之间的相互作用。在进入外周T细胞库之前，胸腺细胞会经历阴性选择，这一过程会消除（或删除）对自身抗原有高亲和力的T细胞，从而促进自身耐受。这些自身抗原包括广泛表达的普遍存在的抗原以及那些表达局限于少数组织的组织特异性抗原（TSA）。TSA在胸腺中的表达主要是髓质胸腺上皮细胞（mTEC）的特性，并且由于这些细胞在介导对普遍存在抗原的阴性选择方面可能不如BM来源的DC，我们研究了这两种细胞类型在对TSA的耐受中的作用。在这里，我们回顾我们的研究，其中我们发现mTEC是对一部分TSA反应性T细胞进行阴性选择的有效介质，而胸腺DC通过从mTEC捕获TSA来扩大经历阴性选择的TSA反应性T细胞的范围。此外，我们最近研究了个体发育过程中对TSA的中枢耐受效率，我们报告这一过程在新生儿中比成年动物效率更低。
