CXC Chemokine Ligand 12 Promotes CCR7-Dependent Naive T Cell Trafficking to Lymph Nodes and Peyer’s Patches

摘要: A number of chemokines, including CCL21, CCL19, CXCL12, and CXCL13, are coexpressed on the lumen or basal lamina high endothelial venules (HEVs) in lymph nodes (LNs) Peyer’s patches (PPs), consistent with idea that they might cooperate to regulate lymphocyte trafficking into these lymphoid tissues. In this study we report acting through its receptor, CXCR4, cooperates CCR7 ligands promote T cell across HEVs. CXCL12 enhanced CCR7-induced chemotaxis wild-type but not CXCR4-deficient cells vitro at suboptimal concentrations a ligand, without affecting expression level ligand-binding ability CCR7. Real-time analysis showed substantially shortened lag time before migration began vitro, speed responding ligand concentrations. addition, augmented ligand-driven ERK phosphorylation actin polymerization under same conditions. adoptive transfer experiments, promoted naive LNs PPs ligand-deficient plt/plt recipient mice; increased was associated binding HEVs their subsequent LN parenchyma. Thus, synergizes by sensitizing thus enabling them respond lower ligands. Such concerted action chemokines provides an additional, previously unknown mechanism for efficient PPs.