6-C-KINE (SLC), A LYMPHOCYTE ADHESION-TRIGGERING CHEMOKINE EXPRESSED BY HIGH ENDOTHELIUM, IS AN AGONIST FOR THE MIP-3-BETA RECEPTOR CCR7

The beta chemokine known as 6-C-kine, secondary lymphoid-tissue chemok ine (SLC), TCA4, or Exodus-2 therein referred to as 6CK/SLC) can trigg er rapid integrin-dependent arrest of lymphocytes rolling under physio logical shear and is highly expressed by high endothelial venules, spe cialized vessels involved in lymphocyte homing from the blood into lym ph nodes and Peyer's patches. We show that 6CK/SLC is an agonist for t he lymphocyte chemoattractant receptor, CCR7 (EBI-1, BLR-2), previousl y described as a receptor for the related beta chemokine MIP-3 beta (E LC or Exodus-3). Moreover, 6CK/SLC and MIP-3 beta attract the same maj or populations of circulating lymphocytes, including naive and memory T cells > B cells (but not natural killer cells); desensitization to M IP-3 beta inhibits lymphocyte chemotaxis to 6CK/SLC but not to the alp ha: chemokine SDF-1 (stromal cell-derived factor); and 6CK/SLC compete s for MIP-3 beta binding to resting mouse lymphocytes. The findings su ggest that the majority of circulating lymphocytes respond to 6CK/SLC and MIP-3 beta in large part through their common receptor CCR7 and th at these molecules may be important mediators of physiological lymphoc yte recirculation in vivo.