Tracing interactions of thymocytes with individual stromal cell partners
Tracing interactions of thymocytes with individual stromal cell partners
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DOI：
10.1002/eji.1830260426
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发表时间：
1996-04-01
影响因子：
5.4
通讯作者：
Merkenschlager, M
中科院分区：
文献类型：
--
作者：
Merkenschlager, M
T细胞发育中的细胞相互作用可以使用体外制备的胸腺嵌合体来分析，其中基质细胞和T细胞前体被分别操纵。在早期的一项研究中，我们发现，对于最佳的T细胞成熟，大多数（如果不是全部的话）基质细胞必须显示适当的（选择）主要组织相容性复合体（MHC）分子：非选择性基质细胞取代选择性导致成熟T细胞产量成比例下降。这些数据表明，选择基质微环境的可用性是正选择的速率限制，并且在正选择中，每个胸腺细胞仅参与一个（而不是多个）基质细胞伴侣。为了验证这一假设，我们开发了一个跟踪系统的胸腺细胞/基质细胞的相互作用，收购的基础上，由胸腺细胞的基质衍生的MHC II类决定簇。当MHC II类缺陷的前体细胞被置于H-2（bxk）F1环境中（所有基质细胞共表达H-2（B）和H-2（k））时，单个胸腺细胞获得两种单倍型的II类决定簇。与此形成鲜明对比的是，当置于镶嵌基质环境中（基质细胞均匀散布表达H-2（B）或H-2（k））时，单个胸腺细胞优先获得一种或另一种单倍型的MHC II类决定簇，但很少同时获得两种决定簇。这提供了强有力的证据表明，胸腺细胞与单个基质细胞有密切的相互作用：在参与一个基质细胞小生境后，胸腺细胞不会（或很少）与其他细胞有混杂的联系。
Cellular interactions in T cell development can be analyzed using thymus chimeras prepared in vitro, in which stromal cells and T cell precursors are manipulated separately. In an earlier study, we showed that for optimal T cell maturation, most-if not all-stromal cells must display appropriate (selecting) major histocompatibility complex (MHC) molecules: the substitution of selecting by nonselecting stromal cells leads to a proportional decrease in mature T cell production. These data imply that the availability of selecting stromal microenvironments is rate limiting for positive selection, and that in positive selection, each thymocyte engages only one (rather than multiple) stromal cell partners. To test this hypothesis, we developed a tracing system for thymocyte/stromal cell interactions, based on the acquisition by thymocytes of stroma-derived MHC class II determinants. When MHC class II-deficient precursors are placed in H-2(bxk) F1 environments (where all stromal cells co-express H-2(b) and H-2(k)), individual thymocytes acquire class II determinants of both haplotypes. In striking contrast, when placed in mosaic stromal environments (where stromal cells express either H-2(b) or H-2(k) evenly interspersed), individual thymocytes preferentially acquire MHC class II determinants of one or the other haplotypes, but rarely both. This provides strong evidence that thymocytes have intimate interactions with individual stromal cells: having engaged one stromal cell niche, thymocytes do not (or only rarely) have promiscuous liaisons with others.