UCSF

While effective adaptive immunity depends on the migration of T cells out of the thymus, the requirements for and sites of thymocyte egress remain incompletely understood. Here, using an intravascular procedure to label emigrating cells, we find that mature single-positive thymocytes predominantly exit via blood vessels at the corticomedullary junction. Sphingosine-1-phosphate receptor-1 (S1P1) transgenic mice demonstrate that S1P1 is the only Kruppel-like factor-2 target necessary for egress. Intravascular labeling experiments aid the identification of roles for Gai3 and CD69 in negatively regulating egress. Finally, we reveal that neural-crest derived pericytes contribute to the sphingosine-1-phosphate that promotes thymic egress. These findings define the major thymic egress route, identify two thymic egress regulators and suggest a novel role for pericytes in promoting reverse transmigration of cells across endothelium.