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The Journal of Immunology, 2000, 164: 639-648.
Copyright © 2000 by The American Association of Immunologists

Murine CCR9, a Chemokine Receptor for Thymus-Expressed Chemokine That Is Up-Regulated Following Pre-TCR Signaling1

Anne M. Norment2,*, Lisa Y. Bogatzki*,{dagger}, Ben N. Gantner* and Michael J. Bevan*,{dagger}

* Department of Immunology and {dagger} Howard Hughes Medical Institute, University of Washington, Seattle WA 98195

Chemokines are likely to play an important role in regulating the trafficking of developing T cells within the thymus. By using anti-CD3{varepsilon} 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-CD3{varepsilon} 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.




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