The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/11/1241/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 9, November 1, 1999 1241-1256

Original Article

Human G Protein–coupled Receptor GPR-9-6/CC Chemokine Receptor 9 Is Selectively Expressed on Intestinal Homing T Lymphocytes, Mucosal Lymphocytes, and Thymocytes and Is Required for Thymus-expressed Chemokine–mediated Chemotaxis

Brian A. Zabela, William W. Agaceb, James J. Campbelld, Heidi M. Heatha, David Parenta, Arthur I. Robertsc, Ellen C. Ebertc, Nasim Kassama, Shixin Qina, Maria Zovkoa, Gregory J. LaRosaa, Li-Li Yanga, Dulce Solera, Eugene C. Butcherd, Paul D. Ponatha, Christina M. Parkerb, and David P. Andrewa
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

Correspondence to: David P. Andrew, LeukoSite, Inc., 215 First St., Cambridge, MA 02142. Tel:617-621-9350 ext. 2250 Fax:617-621-9380 E-mail: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 {alpha}4ß7high 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 {alpha}4ß7-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, {alpha}4ß7, cutaneous lymphocyte antigen, memory, intestinal


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