EBI1-ligand chemokine(ELC)attracts a broad spectrum of lymphocytes: activated T cells strongly up-regulate CCR7 and efficiently migrate toward ELC

• Published in: International immunology Vol. 10; no. 7; pp. 901 - 910
• Main Author: Yoshida, R
• Format: Journal Article
• Language: English
• Published: England Oxford Publishing Limited (England) 01.07.1998
• Subjects: Adult; B cells; Cell Movement - physiology; chemokine; Chemokine CCL19; chemokine receptor; Chemokines, CC - physiology; Chemotactic Factors - biosynthesis; Chemotactic Factors - metabolism; Chemotactic Factors - physiology; chemotaxis; Chemotaxis, Leukocyte - physiology; homing; Humans; In Situ Hybridization; Lymphocyte Activation - physiology; Lymphocytes; Receptors, CCR7; Receptors, Chemokine - biosynthesis; Receptors, Chemokine - metabolism; Receptors, Chemokine - physiology; RNA, Messenger - metabolism; T cells; T-Lymphocytes - immunology; T-Lymphocytes - physiology; Up-Regulation - physiology
• DOI: 10.1093/intimm/10.7.901
• ISSN: 0953-8178; 1460-2377

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 originally identified as an Epstein-Barr virus (EBV)-inducible gene. Here we examined chemotactic activity of ELC on peripheral blood leukocytes. ELC attracted both CD4+ and CD8+ T cells, particularly efficiently after activation with IL-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 also induced vigorous calcium mobilization in T cells stimulated with IL-2 with an ED50 of 3 nM. ELC fused with the secreted form of alkaline phosphatase (ELC-SEAP) specifically bound to lymphocytes and this binding was blocked only by ELC among 10 CC chemokines so far tested. Notably, lymphocytes stimulated with IL-2 or T cells expanded by PHA plus IL-2 showed much higher levels of binding than fresh lymphocytes. Consistently, CCR7 mRNA was detected in CD4+ and CD8+ T cells as well as B cells, but not in NK cells, 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 mRNA was expressed in various lymphoid tissues. By in situ hybridization, ELC and CCR7 mRNA were detected in the parafollicular and inner cortical regions of a lymph node, and in the parafollicular regions of an appendix. Collectively, ELC and CCR7 may be involved in the trafficking of a broad spectrum of lymphocytes, especially activated T cells, into and within various lymphoid tissues.