The chemokine SLC is expressed in T cell areas of lymph nodes and mucosal lymphoid tissues and attracts activated T cells via CCR7.
Secondary lymphoid-tissue chemokine, SLC, also known as exodus-2 and 6Ckine, is a novel CC chemokine with selectivity for T lymphocytes and preferential expression in lymphoid tissues. We have studied its production, receptor usage and biological activities. High levels of SLC mRNA were detected in lymph nodes, the gastrointestinal tract and several gland tissues, but no expression was found by Northern blot analysis in freshly isolated or stimulated blood monocytes and lymphocytes, or neutrophils and eosinophils. In situ hybridization revealed constitutive expression of SLC in the T cell areas and the marginal zone of follicles in lymph nodes and the mucosa-associated lymphoid tissue, but not in B cell areas or sinuses. Comparison with immunocytochemical staining showed similarity between the in situ expression of SLC and the distribution of interdigitating dendritic cells but not with sinus-lining dendritic cells, macrophages or T lymphocytes. SLC induced chemotaxis of T lymphocytes and its activity increased considerably when the cells were conditioned with IL-2 or phytohemagglutinin (PHA). Under optimal conditions SLC had unusually high efficacy and induced the migration of up to 50 % of input T lymphocytes. SLC also induced Ca2+ mobilization in these cells. Similar responses were obtained with EBI1 ligand chemokine (ELC), and sequential stimulation with both chemokines led to cross-desensitization, suggesting that SLC acts via the ELC receptor, CCR7. This was confirmed using murine pre-B cells stably transfected with CCR7 which bound SLC with high affinity and showed chemotaxis and Ca2+ mobilization in response to both SLC and ELC. In T lymphocytes PHA and IL-2, which enhanced chemotactic responsiveness, also markedly enhanced CCR7 expression. In contrast to all known chemokine receptors, up-regulation of CCR7 by IL-2 was transient. A maximum was reached in 2-3 days and expression returned to initial levels within 8-10 days. The present study shows that SLC is constitutively produced within the T cell areas of secondary lymphoid organs and attracts T lymphocytes via CCR7.
Willimann
K
K
Theodor-Kocher Institute, University of Bern, Switzerland.
Legler
D F
DF
Loetscher
M
M
Roos
R S
RS
Delgado
M B
MB
Clark-Lewis
I
I
Baggiolini
M
M
Moser
B
B
D000818:Animals; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000096:biosynthesis*; D002634:Chemotaxis, Leukocyte; D006801:Humans; D017403:In Situ Hybridization; D008024:Ligands; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000276:immunology*; D051379:Mice; D009092:Mucous Membrane / Q000276:immunology; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
C515478:CCL21 protein, human; C515370:CCR7 protein, human; C515479:Ccl21c protein, mouse; C515371:Ccr7 protein, mouse; D054421:Chemokine CCL21; D019742:Chemokines, CC; D008024:Ligands; D054400:Receptors, CCR7; D019707:Receptors, Chemokine