CCR7 and CCR9 in T Cell Development and Trafficking

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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.