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Original Article

^a LeukoSite, Inc., Cambridge, Massachusetts 02142
^b Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115
^c Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903
^d Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University Medical School, Stanford, California 94305
LeukoSite, Inc., 215 First St., Cambridge, MA 02142.617-621-9380617-621-9350 ext. 2250

dpandrew{at}hotmail.com

TECK (thymus-expressed chemokine), a recently described CC chemokine expressed in thymus and small intestine, was found to mediate chemotaxis of human G protein–coupled receptor GPR-9-6/L1.2 transfectants. This activity was blocked by anti–GPR-9-6 monoclonal antibody (mAb) 3C3. GPR-9-6 is expressed on a subset of memory 4β7^high intestinal trafficking CD4 and CD8 lymphocytes. In addition, all intestinal lamina propria and intraepithelial lymphocytes express GPR-9-6. In contrast, GPR-9-6 is not displayed on cutaneous lymphocyte antigen–positive (CLA⁺) memory CD4 and CD8 lymphocytes, which traffic to skin inflammatory sites, or on other systemic 4β7^–CLA^– memory CD4/CD8 lymphocytes. The majority of thymocytes also express GPR-9-6, but natural killer cells, monocytes, eosinophils, basophils, and neutrophils are GPR-9-6 negative. Transcripts of GPR-9-6 and TECK are present in both small intestine and thymus. Importantly, the expression profile of GPR-9-6 correlates with migration to TECK of blood T lymphocytes and thymocytes. As migration of these cells is blocked by anti–GPR-9-6 mAb 3C3, we conclude that GPR-9-6 is the principal chemokine receptor for TECK. In agreement with the nomenclature rules for chemokine receptors, we propose the designation CCR-9 for GPR-9-6. The selective expression of TECK and GPR-9-6 in thymus and small intestine implies a dual role for GPR-9-6/CCR-9, both in T cell development and the mucosal immune response.

Key Words: chemokine • 4β7 • cutaneous lymphocyte antigen • memory • intestinal

Abbreviations used in this paper: CLA, cutaneous lymphocyte–associated antigen; G3PDH, glyceraldehyde 3-phosphate dehydrogenase; GPR, human G protein–coupled receptor; HEV, high endothelial venule; IEL, intraepithelial lymphocyte; IP-10, IFN-–inducible 10-kD protein; I-TAC, IFN-inducible T cell chemoattractant; LPL, lamina propria lymphocyte; MCP, monocyte chemoattractant protein; MDC, macrophage-derived chemokine; MIG, monokine induced by IFN-; MIP, macrophage inflammatory protein; RANTES, regulated upon activation, normal T cell expressed and secreted protein; SDF, stromal cell–derived factor; TARC, thymus and activation-regulated chemokine; TECK, thymus-expressed chemokine.

B.A. Zabel and W.W. Agace contributed equally to this work.

© 1999 The Rockefeller University Press

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