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

• Published in: The Journal of experimental medicine Vol. 206; no. 2; pp. 275 - 285
• Main Authors: Haines, Christopher J, Giffon, Thierry D, Lu, Li-Sheng, Lu, Xiaowei, Tessier-Lavigne, Marc, Ross, Douglas T, Lewis, David B
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 16.02.2009
• Subjects: Age Factors; Animals; Biomarkers; Brief Definitive Report; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell Adhesion Molecules - metabolism; Cell Movement - immunology; CHO Cells; Cricetinae; Cricetulus; DNA Primers - genetics; Flow Cytometry; Humans; Immunity, Cellular - immunology; Immunophenotyping; Receptor Protein-Tyrosine Kinases - metabolism; Thymus Gland - cytology; Thymus Gland - immunology
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20080996

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.