J. Cell Biol., Volume 141, Number 4, May 18, 1998 1053-1059

6-C-kine (SLC), a Lymphocyte Adhesion-triggering Chemokine Expressed by High Endothelium, Is an Agonist for the MIP-3 Receptor CCR7

James J. Campbell,^* Edward P. Bowman,^* Kristine Murphy,^§ Kenneth R. Youngman,^* Michael A. Siani, Darren A. Thompson, Lijun Wu,^§ Albert Zlotnik,^¶ and Eugene C. Butcher^*

^* Laboratory of Immunology and Vascular Biology, Department of Pathology; and The Digestive Disease Center, Department of Medicine, Stanford University Medical School, Stanford, California 94305;  The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304; ^§ LeukoSite, Inc., Cambridge, Massachusetts 02142;  Gryphon Sciences, South San Francisco, California 94080; and ^¶ Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304

The  chemokine known as 6-C-kine, secondary lymphoid-tissue chemokine (SLC), TCA4, or Exodus-2 (herein referred to as 6CK/SLC) can trigger rapid integrin-dependent arrest of lymphocytes rolling under physiological shear and is highly expressed by high endothelial venules, specialized vessels involved in lymphocyte homing from the blood into lymph nodes and Peyer's patches. We show that 6CK/SLC is an agonist for the lymphocyte chemoattractant receptor, CCR7 (EBI-1, BLR-2), previously described as a receptor for the related  chemokine MIP-3 (ELC or Exodus-3). Moreover, 6CK/SLC and MIP-3 attract the same major populations of circulating lymphocytes, including naive and memory T cells > B cells (but not natural killer cells); desensitization to MIP-3 inhibits lymphocyte chemotaxis to 6CK/SLC but not to the  chemokine SDF-1 (stromal cell-derived factor); and 6CK/SLC competes for MIP-3 binding to resting mouse lymphocytes. The findings suggest that the majority of circulating lymphocytes respond to 6CK/SLC and MIP-3 in large part through their common receptor CCR7 and that these molecules may be important mediators of physiological lymphocyte recirculation in vivo.

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