CCR7 and CCR9 in T Cell Development and Trafficking

描述（由申请人提供）：受体CCR 7和CCR 9在胸腺细胞以及外周T细胞上受到动态调节。它们的配体SLC/ELC和TECK分别在胸腺和外周的不同微环境中表达。SLC和ELC在胸腺的皮髓质交界处的小血管上表达，而TECK由皮质上皮细胞产生。CCR 7在成熟的单阳性胸腺细胞上表达，而CCR 9在双阳性胸腺细胞上上调。因此，CCR 7和CCR 9被认为指导这些不同的胸腺细胞亚群通过胸腺的运输。此外，CCR 7、CCR 9及其配体在外周中的表达模式提示在成熟T细胞迁移的调节中起作用。CCR 7在初始和中枢记忆T细胞上表达，但在外周效应记忆T细胞上下调。SLC和ELC在次级淋巴组织的T细胞区中表达。这些表达模式表明CCR 7在次级淋巴器官中T细胞的保留中的作用。相反，CCR 9在固有层和上皮内T细胞上表达，其配体TECK由小肠内衬的内皮细胞表达。因此，提出CCR 9在靶向淋巴细胞迁移至小肠中起作用。然而，这些建议的功能是基于相关的数据。 我们将产生T细胞过度表达CCR 7或CCR 9的转基因小鼠。然后，我们将跟踪和分析胸腺细胞和外周T细胞的迁移。希望这些研究将阐明CCR 7和CCR 9在胸腺细胞和外周T细胞运输中的体内功能。

DESCRIPTION (provided by the applicant): The receptors CCR7 and CCR9 are dynamically regulated on thymocytes as well as on peripheral T cells. Their ligands SLC/ELC and TECK, respectively, are expressed in distinct microenvironments within the thymus and periphery. SLC and ELC are expressed on small vessels at the corticomedullary junction of the thymus, while TECK is produced by cortical epithelial cells. CCR7 is expressed on mature single positive thymocytes, while CCR9 is up-regulated on double positive thymocytes. Thus, CCR7 and CCR9 are thought to direct the trafficking of these distinct thymocyte subpopulations through the thymus. In addition, the expression patterns of CCR7, CCR9, and their ligands in the periphery are suggestive of a role in the regulation of mature T cell migration. CCR7 is expressed on naive and central memory T cells, but is down-regulated on peripheral effector memory T cells. SLC and ELC are expressed in the T cell zone of secondary lymphoid tissues. These expression patterns suggest a role for CCR7 in the retention of T cells in secondary lymphoid organs. In contrast, CCR9 is expressed on lamina propria and intraepithelial T cells and its ligand, TECK is expressed by endothelial cells lining the small intestine. Thus, CCR9 is proposed to function in targeting lymphocyte migration to the small intestine. However, these proposed functions are based on correlative data. We will generate transgenic mice whose T cells over-express either CCR7 or CCR9. We will then track and analyze the migration of both thymocytes and peripheral T cells. It is hoped that these studies will elucidate the in vivo function of CCR7 and CCR9 in thymocyte and peripheral T cell trafficking.