Can bone marrow-derived thymic stromal cells mediate the positive selection of class I-restricted T cells?
Can bone marrow-derived thymic stromal cells mediate the positive selection of class I-restricted T cells?
复制标题
骨髓来源的胸腺基质细胞能否介导 I 类限制性 T 细胞的阳性选择？
DOI：
10.1006/cimm.1996.0175
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发表时间：
1996
影响因子：
4.3
通讯作者：
D. Pardoll
中科院分区：
文献类型：
--
作者：
M. Fort;D. Pardoll
表达自身抗体的T淋巴细胞的阳性选择。MHC限制性T细胞受体由表达于胸腺基质上的MHC分子介导。在这个过程中更有争议的方面是MHC分子对上皮细胞与骨髓源性基质细胞（BM-APC）的相对作用。对于CD 4 + T细胞，大量证据表明，阳性选择仅由胸腺上皮细胞上表达的MHC II类分子驱动。相反，最近的实验已经被解释为显示CD 8 + T细胞发育可以由BM-APC以及上皮细胞上表达的MHC I类分子驱动。为了直接解决这个问题，我们研究了在内源性TCR基因重排缺陷的小鼠中表达转基因、MHC I类限制性TCR的T细胞的发育。由于转基因TCR是唯一表达的TCR，因此该系统对于检测T细胞发育中甚至无效的事件都是极其敏感和特异的。我们的实验表明，MHC I类分子仅在BM-APC上表达，不能驱动CD 8 + T细胞的阳性选择。这一发现，与早期的实验MHC II类，表明胸腺上皮细胞在介导积极选择的定性独特的功能。
Positive selection of T lymphocytes expressing self. MHC-restricted T cell receptors is mediated by MHC molecules expressed on thymic stroma. Among the more controversial aspects of this process is the relative role of MHC molecules on epithelial versus bone marrow-derived stromal elements (BM-APC). For CD4+ T cells, the weight of evidence suggests that positive selection is driven solely by MHC class II molecules expressed on thymic epithelial cells. In contrast, recent experiments have been interpreted to show that CD8+ T cell development can be driven by MHC class I molecules expressed on BM-APCs as well as epithelial cells. To directly address this issue, we have examined the development of T cells expressing a transgenic, MHC class I-restricted TCR in mice deficient in the rearrangement of endogenous TCR genes. Since the transgenic TCR is the only TCR expressed, this system is extremely sensitive and specific for detecting even inefficient events in T cell development. Our experiments demonstrate that MHC class I expression exclusively on BM-APC is incapable of driving positive selection of CD8+ T cells. This finding, together with earlier experiments for MHC class II, suggests a qualitatively unique function of thymic epithelial cells in mediating positive selection.