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 αβ–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-γ than PTK7− naive CD4+ T cells after αβ-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.
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