Owen J J, Jenkinson E J
Department of Anatomy, Medical School, University of Birmingham, UK.
Ann N Y Acad Sci. 1992 Nov 21;663:305-10. doi: 10.1111/j.1749-6632.1992.tb38673.x.
Thymic tolerance depends on induction of apoptosis (programmed cell death) in immature thymocytes by antigen/MHC complexes on dendritic cells (and possibly other bone marrow-derived APCs). Interactions with antigen/MHC complexes on thymic epithelial cells promote maturation of double-positive thymocytes to single-positive cells. However, the nature of the antigen/MHC complexes on thymic epithelial cells is unknown, and if the stromal cell interaction model as just outlined is correct, then presumably these complexes must be different from those presented on dendritic cells, otherwise all cells signaled for positive selection would be subject to negative selection by similar complexes on APCs. The nature of the signals provided by thymic epithelial cells versus dendritic cells is unknown and may provide a key to understanding the processes of positive and negative selection within the thymus. Clearly the intense selection of the T-cell repertoire within the thymus explains the high level of cell death observed within the immature thymocyte compartment. Such intensive selection shapes the T-cell repertoire in a way that provides an explanation for the genetic basis of immune responsiveness and for the susceptibility of certain individuals to autoimmunity.
胸腺耐受性取决于树突状细胞（可能还有其他骨髓来源的抗原呈递细胞）上的抗原/主要组织相容性复合体（MHC）诱导未成熟胸腺细胞发生凋亡（程序性细胞死亡）。与胸腺上皮细胞上的抗原/MHC复合体相互作用可促进双阳性胸腺细胞成熟为单阳性细胞。然而，胸腺上皮细胞上抗原/MHC复合体的性质尚不清楚，如果刚刚概述的基质细胞相互作用模型正确，那么推测这些复合体一定不同于树突状细胞上呈现的复合体，否则所有被信号诱导进行阳性选择的细胞都会被抗原呈递细胞上类似的复合体进行阴性选择。胸腺上皮细胞与树突状细胞提供的信号性质尚不清楚，这可能是理解胸腺内阳性和阴性选择过程的关键。显然，胸腺内对T细胞库的严格选择解释了在未成熟胸腺细胞区室中观察到的高水平细胞死亡。这种严格的选择塑造了T细胞库，为免疫反应性的遗传基础以及某些个体对自身免疫的易感性提供了解释。
