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

• Published in: The Journal of immunology (1950) Vol. 164; no. 2; pp. 639 - 648
• Main Authors: Norment, Anne M, Bogatzki, Lisa Y, Gantner, Ben N, Bevan, Michael J
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15-01-2000
• Subjects: Animals; Antibodies, Monoclonal - pharmacology; Calcium - metabolism; CCR9 protein; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Line; Cell Movement - immunology; Chemokines, CC - metabolism; Chemokines, CC - physiology; Chemotaxis, Leukocyte - immunology; DNA-Binding Proteins - deficiency; DNA-Binding Proteins - genetics; Mice; Mice, Inbred C57BL; Mice, Transgenic; Receptors, Antigen, T-Cell - immunology; Receptors, Antigen, T-Cell - physiology; Receptors, CCR; Receptors, Chemokine - biosynthesis; Receptors, Chemokine - genetics; Signal Transduction - immunology; Stem Cells - metabolism; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; TECK protein; Thymus Gland - cytology; Thymus Gland - metabolism; Transfection; Up-Regulation - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.164.2.639

Chemokines are likely to play an important role in regulating the trafficking of developing T cells within the thymus. By using anti-CD3varepsilon 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-CD3varepsilon 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.