Human CD4 + T cell recent thymic emigrants are identified by protein tyrosine kinase 7 and have reduced immune function

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.