Visualization of CD4/CD8 T cell commitment
Visualization of CD4/CD8 T cell commitment
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DOI：
10.1084/jem.188.12.2321
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发表时间：
1998-12-21
影响因子：
15.3
通讯作者：
Mathis, D
中科院分区：
文献类型：
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作者：
Chan, S;Correia-Neves, M;Mathis, D
描述了一种无害化可视化T细胞谱系承诺的系统。使用“敲入”方法，我们产生了表达β -半乳糖苷酶报告基因的小鼠，以取代CD4；在这些动物中-半乳糖苷酶的表达似乎是CD4基因转录的一个准确的早期指标。我们利用这种敲入序列来追踪胸腺中的CD4/CD8谱系，避免了过去实验方法的重要缺陷。我们的结果支持胸腺细胞参与的选择性模型，证明了一个基本的对称过程：分化的CD4(+)CD8（+）细胞参与任何一类主要组织相容性复合体（MHC）分子都可以产生任何谱系的T细胞抗原受体（TCK）（hi）胸腺细胞。主要发现包括(a)直接证明了大量的CD4-committed，受体/辅助受体错配的细胞在MHC ii类缺陷小鼠中，这是对选择性模型的关键预测，(b)通过在TCK转基因系中强制表达CD8来高效地拯救这种“错配”中间体，并解释了为什么以前的这种性质的实验不太成功-这是过去对选择性模型的主要批评；(c)直接证明在i类缺陷动物中存在类似的cd8错配中间体群体，尽管规模较小。最后，我们没有发现CD4默认途径的证据。
A system to innocuously visualize T cell lineage commitment is described. Using a "knock-in" approach, we have generated mice expressing a beta-galactosidase reporter in place of CD4; expression of beta-galactosidase in these animals appears to be an accurate,Ind early indicator of CD4 gene transcription. We have exploited this knock-in line to trace CD4/CD8 lineage commitment in the thymus, avoiding important pitfalls of past experimental approaches. Out results argue in favor of a selective model of thymocyte commitment, demonstrating a fundamentally: symmetrical process: engagement of either class of major histocompatibility complex (MHC) molecule by a differentiating CD4(+)CD8(+) cell can give rise to T cell antigen receptor (TCK)(hi) thymocytes of either lineage. Key findings include (a) direct demonstration of a substantial number of CD4-committed, receptor/coreceptor-mismatched cells ill MHC, class II-deficient mice, a critical prediction of the selective model, (b) highly efficient rescue of such "mismatched" intermediates by forced expression of CD8 in a TCK transgenic line, and an explanation of why previous experiments of this nature were less successful-a major past criticism of the selective model; (c) direct demonstration of an analogous, though smaller, population of CD8-committed mismatched intermediates in class I-deficient animals. Finally, we found no evidence of a CD4 default pathway.