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Chemokine receptor CCR7 required for T lymphocyte exit from peripheral tissues

Nature Immunology volume 6, pages 889–894 (2005)Cite this article

Abstract

Lymphocytes travel throughout the body to carry out immune surveillance and participate in inflammatory reactions. Their path takes them from blood through tissues into lymph and back to blood. Molecules that control lymphocyte recruitment into extralymphoid tissues are well characterized, but exit is assumed to be random. Here, we showed that lymphocyte emigration from the skin was regulated and was sensitive to pertussis toxin. CD4+ lymphocytes emigrated more efficiently than CD8+ or B lymphocytes. T lymphocytes in the afferent lymph expressed functional chemokine receptor CCR7, and CCR7 was required for T lymphocyte exit from the skin. The regulated expression of CCR7 by tissue T lymphocytes may control their exit, acting with recruitment mechanisms to regulate lymphocyte transit and accumulation during immune surveillance and inflammation.

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Figure 1: Tissue exit is nonrandom.
Figure 2: Tissue exit involves Gαi protein–coupled receptor signaling.
Figure 3: T cells require expression of CCR7 to exit the skin and reach the draining lymph node.
Figure 4: Transduction of CCR7 rescues Ccr7−/− CD4+ T cell exit from the skin and migration to the draining lymph node.
Figure 5: Ovine T cells in the afferent lymph express functional CCR7.

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Acknowledgements

We thank D. Campbell (University of Washington) for comments on the manuscript, and M. Zasio for sheep blood. Supported by the National Institutes of Health, the Department of Veterans Affairs (E.C.B.), the FACS Core of the Stanford Digestive Disease Center (National Institutes of Health P30 DK56339), Howard Hughes Medical Institute (C.N.A.), the Arthritis Foundation (G.F.D.) and Deutsche Forschungsgemeinschaft (G.F.D.).

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Authors and Affiliations

  1. Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, 94305, California, USA

    Gudrun F Debes, Carrie N Arnold & Eugene C Butcher

  2. Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, 94304, California, USA

    Gudrun F Debes, Carrie N Arnold & Eugene C Butcher

  3. Center for Infectious Disease Research and Vaccinology, South Dakota State University, Brookings, 57007, South Dakota, USA

    Alan J Young

  4. Department of Nephrology and Hypertension, University of Schleswig-Holstein, Campus Kiel, Kiel, 24105, Germany

    Stefan Krautwald

  5. Department of Tumor Genetics and Immunogenetics, Max-Delbrück Center for Molecular Medicine, Berlin, 13125, Germany

    Martin Lipp

  6. Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, M5S 1A8, Ontario, Canada

    John B Hay

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  1. Gudrun F Debes
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Correspondence to Gudrun F Debes.

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Debes, G., Arnold, C., Young, A. et al. Chemokine receptor CCR7 required for T lymphocyte exit from peripheral tissues. Nat Immunol 6, 889–894 (2005). https://doi.org/10.1038/ni1238

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