CC chemokine receptor 7 contributes to Gi-dependent T cell motility in the lymph node.
Naive T cells migrate extensively within lymph node (LN) T zones to scan for Ag-bearing dendritic cells. However, the extracellular signals controlling T cell motility in LNs are not well defined. In this study, by real-time imaging of LNs, we show that the inhibition of Gi signaling in T cells severely impairs their migration. The chemokine CCL21, a ligand of CCR7, strongly induces chemokinesis in vitro, and T cell motility in LNs from CCR7 ligand-deficient plt/plt mice was reduced. CCR7-deficient T cells in wild-type LNs showed a similar reduction in motility, and antagonism of CXCR4 function did not further decrease their motility. The effect of CCR7 or CCR7-ligand deficiency could account for approximately 40% of the Gi-dependent motility. These results reveal a role for CCR7 in promoting T cell migration within lymphoid organ T zones, and they suggest the additional involvement of novel Gi-coupled receptors in promoting T cell motility at these sites.
Okada
Takaharu
T
Department of Microbiology and Immunology and Howard Hughes Medical Institute, University of California-San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
Cyster
Jason G
JG
D000818:Animals; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000172:deficiency / Q000276:immunology*; D002633:Chemotaxis / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D051379:Mice; D036641:Microscopy, Fluorescence, Multiphoton; D054398:Receptors, CCR4; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000172:deficiency / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
C515479:Ccl21c protein, mouse; C515355:Ccr4 protein, mouse; C515371:Ccr7 protein, mouse; D054421:Chemokine CCL21; D019742:Chemokines, CC; D054398:Receptors, CCR4; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D019206:GTP-Binding Protein alpha Subunits, Gi-Go