Discrimination between thymic epithelial cells and peripheral antigen-presenting cells in the induction of immature T cell differentiation.
Discrimination between thymic epithelial cells and peripheral antigen-presenting cells in the induction of immature T cell differentiation.
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胸腺上皮细胞和外周抗原呈递细胞在诱导未成熟 T 细胞分化中的区别。
DOI：
10.1016/1074-7613(94)90069-8
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发表时间：
1994
期刊：
影响因子：
32.4
通讯作者：
Kaye,J
中科院分区：
文献类型：
--
作者：
Poirier,G;Lo,D;Reilly,CR;Kaye,J
在胸腺内迁移过程中，表达能够识别所表达的MHC分子的TCR的未成熟的CD4+CD8+胸腺细胞被积极选择，即完成其分化程序，成为成熟的T细胞。利用在培养中可以被诱导分化的未成熟的CD4+CD8+T细胞系DPK，我们在这里展示了分离的胸腺上皮细胞亚群可以诱导分化，但不是外周抗原提呈细胞，这表明这些细胞在T细胞发育中具有独特的功能。此外，胸腺上皮细胞对特异性抗原诱导的激活标志物的分析首次直接证明阳性选择与低水平的细胞激活有关。与胸腺选择的严格亲和力-亲和力模型不同，我们认为特殊的抗原提呈细胞环境是胸腺TCR介导的分化的重要贡献者。T细胞发育的一个关键时刻是将未成熟的CD4+CD8+T细胞分化为功能成熟的CD4+CD8-或CD4-CD8+T细胞。这一步骤被称为正选择，需要T细胞受体(TCR)识别胸腺皮质中抗原提呈细胞上表达的主要组织相容性复合体(MHC)分子。在没有外源性外源多肽的情况下，CD4+CD8+未成熟胸腺细胞是如何被触发分化的，而成熟的T细胞则需要识别与MHC分子结合的外源抗原才能激活，目前仍不清楚。由于成熟T细胞的激活和未成熟T细胞的分化是在不同的微环境中发生的，因此抗原提呈细胞的特化或T细胞的分化状态可能在这种二分法中起作用。使用骨髓嵌合体(Zinkernagel等人，1978；Bevan和Fink，1978；Lo和Sprent，1986)、在胸腺上皮(TE)细胞子集上表达MHC分子的转基因小鼠(Benoist和Mathis，1989；Berg等人，1989)、纯化TE细胞(Jenkinson等人，1992)或TE细胞系(Vukmanovic等人，1992；Hugo等人，1992)的实验已经确定皮质上皮细胞可能是阳性选择的抗原提呈细胞。然而，TE细胞是否与外周淋巴器官中发现的抗原提呈细胞在功能上不同，这些研究并没有直接解决。其他报告表明，造血细胞(Bix和RAULET，1992)，或成纤维细胞
During their intrathymic migration, immature CD4+ CD8+ thymocytes that express a TCR able to recognize the expressed MHC molecules are positively selected, ie, complete their differentiation program and become mature T cells. Using the immature CD4+ CD8+ T cell line DPK, which can be Induced to differentiate in culture, we show here that a subset of isolated thymic epithelial cells, but not peripheral antigen-presenting cells, can induce differentiation, suggesting a unique function of these cells in T cell development. In addition, analysis of activation markers induced by thymic epithelial cells versus specific antigen gives the first direct evidence that positive selection is associated with low level cell activation. In contrast with strict affinity-avldity models of thymic selection, we propose that a specialized antigen-presenting cell environment is an essential contributor to TCR-mediated differentiation in the thymus. introductionOne critical juncture in T cell development is defined by the differentiation of immature CD4+ CD8+ T cells into functionally mature CD4+ CD8-or CD4-CD8+ Tcells. This step, called positive selection, requires the recognition by the T cell receptor (TCR) of major histocompatibility complex (MHC) molecules expressed on antigen-presenting cells residing in the thymic cortex. How CD4+ CD8+ immature thymocytes are triggered to differentiate in the absence of exogenous foreign peptides, while mature T cells require recognition of foreign antigen bound to MHC molecules for activation, is still unclear. Since mature T cell activation and immature T cell differentiation take place in distinct microenvironments, it is possible that specialization of the antigen-presenting cell or the differentiation state of the T cell could play a role in this dichotomy. Experiments using bone marrow chimeras (Zinkernagel et al., 1978; Bevan and Fink, 1978; Lo and Sprent, 1986), transgenic mice expressing MHC molecules on a subset of thymic epithelial (TE) cells (Benoist and Mathis, 1989; Berg et al., 1989), purified TE cells (Jenkinson et al., 1992), or TE cell lines (Vukmanovic et al., 1992; Hugo et al., 1992) have identified the cortical epithelial cell as the likely antigenpresenting cell for positive selection. Whether TE cells differ functionally from antigen-presenting cells found in peripheral lymphoid organs, however, was not directly addressed by these studies. Other reports have shown that hematopoietic cells (Bix and Raulet, 1992), or fibroblasts