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 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.
Shionogi Institute for Medical Science, Osaka, Japan.
R
R
Yoshida
M
M
Nagira
T
T
Imai
M
M
Baba
S
S
Takagi
Y
Y
Tabira
J
J
Akagi
H
H
Nomiyama
O
O
Yoshie
D000328:Adult; D002465:Cell Movement / Q000502:physiology; D054415:Chemokine CCL19; D019742:Chemokines, CC / Q000502:physiology*; D002630:Chemotactic Factors / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D008213:Lymphocyte Activation / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
C515460:CCL19 protein, human; C515370:CCR7 protein, human; D054415:Chemokine CCL19; D019742:Chemokines, CC; D002630:Chemotactic Factors; D012333:RNA, Messenger; D054400:Receptors, CCR7; D019707:Receptors, Chemokine