On the role of thymic epithelium vs. bone marrow-derived cells in repertoire selection of T cells.
On the role of thymic epithelium vs. bone marrow-derived cells in repertoire selection of T cells.
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胸腺上皮与骨髓来源细胞在 T 细胞库选择中的作用。
DOI：
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发表时间：
1999
影响因子：
11.1
通讯作者：
A. Althage
中科院分区：
文献类型：
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作者：
R. Zinkernagel;A. Althage
T淋巴细胞在胸腺中成熟成为功能性T细胞。嵌合小鼠和T细胞受体（TCR）转基因（tg）小鼠的研究表明，主要组织相容性基因复合体（MHC）的胸腺放射抗性（假定为上皮）细胞积极选择的MHC限制性T细胞库。令人惊讶的是，没有用MHC不相容的胸腺重建的胸腺的小鼠产生效应T细胞，其通常对宿主特异性而不是对胸腺MHC特异性。本研究重新分析了这一长期存在的矛盾，在裸鼠与MHC不相容的胸腺加上或减去免疫缺陷的骨髓来源的细胞或在裸鼠表达转基因T细胞受体重建。揭示了胸腺依赖性但胸腺MHC非依赖性T细胞成熟的途径，其中抗病毒T细胞库的扩增依赖于骨髓源性细胞的MHC。这些结果表明，一个替代的，如果不是一个一般的，T细胞成熟和选择的途径：胸腺可能基本上作为一个器官，促进T细胞受体的表达，T细胞的特异性，但是，反映了库扩展加上细胞存活和效应T细胞诱导驱动的MHC的骨髓来源的细胞。因此，纯胸腺缺陷可以通过同种和异种胸腺移植有效重建。
T lymphocytes mature in the thymus to become functional T cells. Studies with chimeric mice and T cell receptor (TCR) transgenic (tg) mice have indicated that the major histocompatibility gene complex (MHC) of thymic radio-resistant (presumed to be epithelial) cells positively select the MHC-restricted T cell repertoire. Surprisingly, mice without a thymus reconstituted with an MHC-incompatible thymus generate effector T cells which are, in general, specific for the host and not for the thymic MHC. The present study reanalyzed this longstanding paradox in nude mice that were reconstituted with an MHC-incompatible thymus plus or minus immunologically defective bone marrow-derived cells or in nude mice expressing a transgenic T cell receptor. A pathway of thymus-dependent but thymic MHC-independent T cell maturation is revealed where expansion of the antiviral T cell repertoire depends on the MHC of bone marrow-derived cells. These results indicate an alternative, if not a general, pathway of T cell maturation and selection: the thymus may function essentially as an organ promoting T cell receptor expression; T cell specificity, however, reflects repertoire expansion plus cell survival and effector T cell induction driven by the MHC of bone marrow-derived cells. Therefore pure thymus defects can be efficiently reconstituted by allo- and xenogeneic thymic grafts.