David B. Lewis

Publication Details

  • Human CD4(+) T cell recent thymic emigrants are identified by protein tyrosine kinase 7 and have reduced immune function JOURNAL OF EXPERIMENTAL MEDICINE Haines, C. J., Giffon, T. D., Lu, L., Lu, X., Tessier-Lavigne, M., Ross, D. T., Lewis, D. B. 2009; 206 (2): 275-285

    Abstract:

    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 alphabeta-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-gamma than PTK7(-) naive CD4(+) T cells after alphabeta-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.

    View details for DOI 10.1084/jem.20080996

    View details for Web of Science ID 000266008800004

    View details for PubMedID 19171767

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