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Science 328 (5982): 1129-1135

Copyright © 2010 by the American Association for the Advancement of Science

Neural Crest–Derived Pericytes Promote Egress of Mature Thymocytes at the Corticomedullary Junction

Marcus A. Zachariah, and Jason G. Cyster*

Abstract: T cell egress from the thymus is essential for adaptive immunity, yet the requirements for and sites of egress are incompletely understood. We have shown that transgenic expression of sphingosine-1-phosphate receptor-1 (S1P1) in immature thymocytes leads to their perivascular accumulation and premature release into circulation. Using an intravascular procedure to label emigrating cells, we found that mature thymocytes exit via blood vessels at the corticomedullary junction. By deleting sphingosine kinases in neural crest–derived pericytes, we provide evidence that these specialized vessel-ensheathing cells contribute to the S1P that promotes thymic egress. Lymphatic endothelial cell–derived S1P was not required. These studies identify the major thymic egress route and suggest a role for pericytes in promoting reverse transmigration of cells across blood vessel endothelium.

Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco, 513 Parnassus Avenue, HSE1001, San Francisco, CA 94143, USA.

* To whom correspondence should be addressed. E-mail: Jason.Cyster{at}ucsf.edu

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