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Department of Microbiology and Immunology and Howard Hughes Medical Institute, University of California, San Francisco, CA 94143
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 
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants AI 45073 and AI 40098, by the Howard Hughes Medical Institute, and by a Sandler New Technology Award. T.O. was supported in part by the Japan Society for Promotion of Science.
2 Address correspondence and reprint requests to Dr. Jason G. Cyster, Department of Microbiology and Immunology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143. E-mail address: jason/cyster{at}ucsf.edu
3 Abbreviations used in this paper: LN, lymph node; DC, dendritic cell; PTX, pertussis toxin; CMTMR, 5-(and-6)-(((4-chloromethyl)benzoyl)amino)tetramethylrhodamine; CMAC, 7-amino-4-chloromethylcoumarin.
4 The online version of this article contains supplemental material.
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