Murine CCR9, a Chemokine Receptor for Thymus-Expressed Chemokine That Is Up-Regulated Following Pre-TCR Signaling

Abstract

Chemokines are likely to play an important role in regulating the trafficking of developing T cells within the thymus. By using anti-CD3ε treatment of recombinase-activating gene 2 (Rag2−/−) mice to mimic pre-TCR signaling and drive thymocyte development to the double positive stage, we have identified murine GPR-9-6 as a chemokine receptor whose expression is strongly 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 produced 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-transfected cells. In addition, TECK stimulates the migration of normal double positive thymocytes, as well as Rag2−/− thymocytes following anti-CD3ε treatment. Hence, GPR-9-6 has been designated as CC chemokine receptor 9 (CCR9). Our results suggest that TECK delivers signals through CCR9 important for the navigation of developing thymocytes.