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Chemokine receptor CCR7 guides T cell exit from peripheral tissues and entry into afferent lymphatics

Nature Immunology volume 6, pages 895–901 (2005)Cite this article

Abstract

T cell circulation between peripheral tissues and the lymphoid compartment is critical for immunosurveillance and host defense. However, the factors that determine whether T cells remain in peripheral tissue or return to the circulation are undefined. Here we demonstrate that the chemokine receptor CCR7 is a critical signal that determines T cell exit from peripheral tissue. Both CCR7− and CCR7+ effector T cells entered mouse asthmatic lung and while CCR7− T cells accumulated, CCR7+ T cells continued to migrate into afferent lymph. Delivery of both CCR7+ and CCR7− T cells directly into the airways showed that only CCR7+ T cells exited the lung and entered draining lymph nodes. Our study establishes a molecular basis for T cell exit from peripheral tissues.

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Figure 1: CCR7− but not CCR7+ CD44hi T cells accumulate in the inflamed lung.
Figure 2: Constitutive T cell transgenic CCR7 expression results in a paucity of T cells in inflamed extralymphoid tissues and accumulation in lymphoid tissues.
Figure 3: CCR7 expression on antigen-specific T cells determines their accumulation in lymphoid versus inflamed extralymphoid tissues.
Figure 4: Adoptively transferred wild-type OT-II or CCR7-transgenic OT-II T cells induce inflammation after challenge with aerosolized OVA.
Figure 5: CCR7 'guides' CD4+ and CD8+ effector T cell exit from peripheral tissues and entry into afferent lymphatics.

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Acknowledgements

We thank members of the Luster laboratory for discussions; and A.M. Tager, P. Sarraf, B.D. Medoff and S.A. Islam for discussions, technical advice and critical reading of the manuscript. Supported by the National Institutes of Health (R01-AI40618 to A.D.L. and F32-AI054107 to S.K.B.).

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  1. Division of Rheumatology, Center for Immunology and Inflammatory Diseases, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Charlestown, 02129, Massachusetts, USA

    Shannon K Bromley, Seddon Y Thomas & Andrew D Luster

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Correspondence to Andrew D Luster.

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Bromley, S., Thomas, S. & Luster, A. Chemokine receptor CCR7 guides T cell exit from peripheral tissues and entry into afferent lymphatics. Nat Immunol 6, 895–901 (2005). https://doi.org/10.1038/ni1240

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