title: 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 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.
authors.affiliation: Department of Pediatrics and the Immunology Program, Stanford University, Stanford, CA 94305, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Haines
authors.forename: Thierry D
authors.initials: TD
authors.lastname: Giffon
authors.forename: Li-Sheng
authors.initials: LS
authors.lastname: Lu
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Lu
authors.forename: Marc
authors.initials: M
authors.lastname: Tessier-Lavigne
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Ross
authors.forename: David B
authors.initials: DB
authors.lastname: Lewis
mesh_terms: D000367:Age Factors; D000818:Animals; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement / Q000276:immunology*; D006224:Cricetinae; D003412:Cricetulus; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D016130:Immunophenotyping; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D017931:DNA Primers; C096905:PTK7 protein, human; D020794:Receptor Protein-Tyrosine Kinases