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 invarious lymphoid tissues and a high-affinity functional ligand forEBI1/CCR7, a seven transmembrane G-protein-coupled receptor originallyidentified as an Epstein-Barr virus (EBV)-inducible gene. Here we examinedchemotactic activity of ELC on peripheral blood leukocytes. ELC attractedboth CD4+ and CD8+ T cells, particularly efficiently after activation withIL-2 or with phytohemagglutinin (PHA) plus IL-2, as well as CD19+ B cells,but not CD16+ NK cells, CD14+ monocytes or neutrophils. Among CD3+ T cells,ELC attracted both CD45RO- naive and CD45RO+ memory subsets. ELC alsoinduced vigorous calcium mobilization in T cells stimulated with IL-2 withan ED50 of 3 nM. ELC fused with the secreted form of alkaline phosphatase(ELC-SEAP) specifically bound to lymphocytes and this binding was blockedonly by ELC among 10 CC chemokines so far tested. Notably, lymphocytesstimulated with IL-2 or T cells expanded by PHA plus IL-2 showed muchhigher levels of binding than fresh lymphocytes. Consistently, CCR7 mRNAwas detected in CD4+ and CD8+ T cells as well as B cells, but not in NKcells, monocytes or neutrophils, and was dramatically increased in T cellsupon treatment with IL-2 or with PHA plus IL-2. Like ELC mRNA, CCR7 mRNAwas expressed in various lymphoid tissues. By in situ hybridization, ELCand CCR7 mRNA were detected in the parafollicular and inner corticalregions of a lymph node, and in the parafollicular regions of an appendix.Collectively, ELC and CCR7 may be involved in the trafficking of a broadspectrum of lymphocytes, especially activated T cells, into and withinvarious lymphoid tissues.