Preferential Chemotaxis and Fugetaxis of CD4−CD8− Thymocytes in Response to CXCL16 (95.8)

Abstract

Abstract Directed migration of developing thymocytes to specific anatomic regions of the thymus can influence normal T cell development. However, the mechanisms which influence migration of early CD4−CD8− (double negative: DN) thymocytes are incompletely understood. We investigated the role of chemokine CXCL16 and its receptor, CXCR6, in thymocyte migration. Gene expression analysis showed that CXCR6 is expressed only in DN thymocytes, but not at later stages of development, whereas CXCL16 is expressed on stromal cells throughout the thymus. The ability of DN thymocytes to migrate in response to CXCL16 was tested with in vitro transwell assays. At concentrations of 100 and 10ng/ml, DN thymocytes demonstrated specific migration toward CXCL16, whereas migration of CD4+CD8+ thymocytes was not significantly different from controls. We also tested the fugetactic ability of DN thymocytes from CXCL16, and observed that DN thymocytes selectively migrated away at concentrations of 10 and 1ng/ml. These data demonstrate that DN thymocytes migrate differentially to CXCL16 in a dose-dependent fashion. Thus, CXCR6 and CXCL16 may be involved in localized cell migration in the thymus. ADAM10 and Notch influence cell migration in other systems; thus experiments to test their roles in the control of CXCR6-mediated migration of DN subsets in the thymus are ongoing. Supported by UCM Faculty Startup Funds