International Immunology, Vol 10, 901-910, Copyright © 1998 by Oxford University Press
R Yoshida, M Nagira, T Imai, M Baba, S Takagi, Y Tabira, J Akagi, H Nomiyama and O Yoshie
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.
ARTICLES
EBI1-ligand chemokine (ELC) attracts a broad spectrum of lymphocytes: activated T cells strongly up-regulate CCR7 and efficiently migrate toward ELC
Shionogi Institute for Medical Science, Osaka, Japan.
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