Mouse TCRαβ+CD8αα intraepithelial lymphocytes express genes that down-regulate their antigen reactivity and suppress immune responses
Mouse TCRαβ+CD8αα intraepithelial lymphocytes express genes that down-regulate their antigen reactivity and suppress immune responses
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DOI：
10.4049/jimmunol.178.7.4230
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发表时间：
2007-04-01
影响因子：
4.4
通讯作者：
Kronenberg, Mitchell
中科院分区：
文献类型：
--
作者：
Denning, Timothy L.;Granger, Steve;Kronenberg, Mitchell
表达 alpha beta TCR 和 CD8 alpha alpha 同二聚体的小鼠小肠上皮内淋巴细胞 (IEL) 是一个神秘的 T 细胞亚群，因为它们的特异性和体内功能仍有待定义。为了深入了解这些细胞的性质，我们使用微阵列分析结合实时定量 PCR 和流式细胞术进行了全局基因表达谱分析。使用这些方法，将TCR alpha beta(+)CD8 alpha alpha IEL与其TCR alpha beta(+)CD8 beta(+)和TCR-gamma delta(+)对应物进行比较。有趣的是，TCR alpha beta(+)CD8 alpha alpha IEL被发现优先表达预期下调其反应性的基因。它们具有 NK 受体 Ly49 家族成员的独特表达模式，并且倾向于表达抑制性受体以及一些激活性受体。 TCR alpha beta(+)CD8 alpha alpha 和 TCR-gamma delta(+) IEL 的信号传导机制与其他 IEL 和外周 T 细胞的构建方式不同，其低水平表达用于激活 T 细胞的连接子和高表达非 T 细胞激活连接子（抑制 T 细胞激活）就证明了这一点。 TCR alpha beta(+)CD8 alpha alpha IEL 亚群还增加了参与免疫调节的基因表达，包括 TGF-beta(3) 和淋巴细胞激活基因 3。总的来说，这些数据强调了这样一个事实：虽然 TCR alpha beta(+)CD8 alpha alpha IEL 类似于 TCR gamma delta(+) IEL，但它们是具有受调节 Ag 反应性的独特细胞群，可能具有调节功能。
Mouse small intestine intraepithelial lymphocytes (IEL) that express alpha beta TCR and CD8 alpha alpha homodimers are an enigmatic T cell subset, as their specificity and in vivo function remain to be defined. To gain insight into the nature of these cells, we performed global gene expression profiling using microarray analysis combined with real-time quantitative PCR and flow cytometry. Using these methods, TCR alpha beta(+)CD8 alpha alpha IEL were compared with their TCR alpha beta(+)CD8 beta(+) and TCR-gamma delta(+) counterparts. Interestingly, TCR alpha beta(+)CD8 alpha alpha IEL were found to preferentially express genes that would be expected to down-modulate their reactivity. They have a unique expression pattern of members of the Ly49 family of NK receptors and tend to express inhibitory receptors, along with some activating receptors. The signaling machinery of both TCR alpha beta(+)CD8 alpha alpha and TCR-gamma delta(+) IEL is constructed differently than other IEL and peripheral T cells, as evidenced by their low-level expression of the linker for activation of T cells and high expression of the non-T cell activation linker, which suppresses T cell activation. The TCR alpha beta(+)CD8 alpha alpha IEL subset also has increased expression of genes that could be involved in immune regulation, including TGF-beta(3) and lymphocyte activation gene-3. Collectively, these data underscore the fact that, while TCR alpha beta(+)CD8 alpha alpha IEL resemble TCR gamma delta(+) IEL, they are a unique population of cells with regulated Ag reactivity that could have regulatory function.