Chemokine receptor CCR7 guides T cell exit from peripheral tissues and entry into afferent lymphatics.
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.
Bromley
Shannon K
SK
Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Thomas
Seddon Y
SY
Luster
Andrew D
AD
D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D008168:Lung / Q000473:pathology; D008196:Lymph / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7; D019707:Receptors, Chemokine