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.