EBI1-LIGAND CHEMOKINE (ELC) ATTRACTS A BROAD-SPECTRUM OF LYMPHOCYTES - ACTIVATED T-CELLS STRONGLY UP-REGULATE CCR7 AND EFFICIENTLY MIGRATE TOWARD ELC

EBI1-ligand chemokine (ELC) is a CC chemokine constitutively expressed in various lymphoid tissues and a high-affinity functional ligand for EBI1/CCR7, a seven transmembrane G-protein-coupled receptor originall y identified as an Epstein-Barr virus (EBV)-inducible gene. Here we ex amined chemotactic activity of ELC on peripheral blood leukocytes. ELC attracted both CD4(+) and CD8(+) T cells, particularly efficiently af ter activation with IL-2 or with phytohemagglutinin (PHA) plus IL-2, a s well as CD19(+) B cells, but not CD16(+) NK cells, CD14(+) monocytes or neutrophils. Among CD3(+) T cells, ELC attracted both CD45RO(-) na ive and CD45RO(+) memory subsets. ELC also induced vigorous calcium mo bilization in T cells stimulated with IL-2 with an ED50 Of 3 nM. ELC f used with the secreted form of alkaline phosphatase (ELC-SEAP) specifi cally bound to lymphocytes and this binding was blocked only by ELC am ong 10 CC chemokines so far tested. Notably, lymphocytes stimulated wi th IL-2 or T cells expanded by PHA plus IL-2 showed much higher levels of binding than fresh lymphocytes. Consistently, CCR7 mRNA was detect ed in CD4(+) and CD8(+) T cells as well as B cells, but not in NK cell s, monocytes or neutrophils, and was dramatically increased in T cells upon treatment with IL-2 or with PHA plus IL-2. Like ELC mRNA, CCR7 m RNA was expressed in various lymphoid tissues. By in situ hybridizatio n, ELC and CCR7 mRNA were detected in the parafollicular and inner cor tical regions of a lymph node, and in the parafollicular regions of an appendix. Collectively, ELC and CCR7 may be involved in the trafficki ng of a broad spectrum of lymphocytes, especially activated T cells, i nto and within various lymphoid tissues.