Murine CCR9, a chemokine receptor for thymus-expressed chemokine that is up-regulated following pre-TCR signaling

Chemokines are likely to play. an important role in regulating the traffick ing bf developing T cells within the thymus. By using anti-CD3 epsilon trea tment of recombinase-activating gene 2 (Rag2(-/-)) mice to mimic pre-TCR si gnaling and drive thymocyte development to the double positive stage, we ha ve identified murine GPR-9-6 as a chemokine receptor whose expression is st rongly induced following pre-TCR signaling. GPR-9-6 mRNA is present at high levels in the thymus, and by RT-PCR analysis its expression is induced as normal thymocytes undergo the double negative to double positive transition . Furthermore we show that TECK (thymus-expressed chemokine), a chemokine p roduced by thymic medullary dendritic cells, is a functional ligand for GPR -9-6, TECK specifically induces a calcium flux and chemotaxis of GPR-9-6-tr ansfected cells. In addition, TECK stimulates the migration of normal doubl e positive thymocytes, as well as Rag2(-/-) thymocytes following anti-CD3 e psilon treatment, Hence, GPR-9-6 has been designated as CC chemokine recept or 9 (CCR9), Our results suggest that TECK delivers signals through CCR9 im portant for the navigation of developing thymocytes.