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¹ Department of Pediatrics and the Immunology Program, ² Department of Biological Sciences and Howard Hughes Medical Institute, and ³ Department of Biochemistry, Stanford University, Stanford, CA 94305

CORRESPONDENCE David B. Lewis: dblewis{at}stanford.edu

CD4⁺ recent thymic emigrants (RTEs) comprise a clinically and immunologically important T cell population that indicates thymic output and that is essential for maintaining a diverse β–T cell receptor (TCR) repertoire of the naive CD4⁺ T cell compartment. However, their frequency and function are poorly understood because no known surface markers distinguish them from older non-RTE naive CD4⁺ T cells. We demonstrate that protein tyrosine kinase 7 (PTK7) is a novel marker for human CD4⁺ RTEs. Consistent with their recent thymic origin, human PTK7⁺ RTEs contained higher levels of signal joint TCR gene excision circles and were more responsive to interleukin (IL)-7 compared with PTK7^– naive CD4⁺ T cells, and rapidly decreased after complete thymectomy. Importantly, CD4⁺ RTEs proliferated less and produced less IL-2 and interferon- than PTK7^– naive CD4⁺ T cells after β-TCR/CD3 and CD28 engagement. This immaturity in CD4⁺ RTE effector function may contribute to the reduced CD4⁺ T cell immunity observed in contexts in which CD4⁺ RTEs predominate, such as in the fetus and neonate or after immune reconstitution. The ability to identify viable CD4⁺ RTEs by PTK7 staining should be useful for monitoring thymic output in both healthy individuals and in patients with genetic or acquired CD4⁺ T cell immunodeficiencies.

X. Lu’s present address is Department of Cell Biology, University of Virginia, Charlottesville, VA 22908.

M. Tessier-Lavigne’s present address is Genentech, Inc., San Francisco, CA 94080.

D. Ross’s present address is Applied Genomics, Inc., Burlingame, CA 94010.

© 2009 Haines et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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