title: NKAP is required for T cell maturation and acquisition of functional competency.
abstract: Newly generated T cells are unable to respond to antigen/MHC. Rather, post-selection single-positive thymocytes must undergo T cell maturation to gain functional competency and enter the long-lived naive peripheral T cell pool. This process is poorly understood, as no gene specifically required for T cell maturation has been identified. Here, we demonstrate that loss of the transcriptional repressor NKAP results in a complete block in T cell maturation. In CD4-cre NKAP conditional knockout mice, thymic development including positive selection occurs normally, but there is a cell-intrinsic defect in the peripheral T cell pool. All peripheral naive CD4-cre NKAP conditional knockout T cells were found to be functionally immature recent thymic emigrants. This defect is not simply in cell survival, as the T cell maturation defect was not rescued by a Bcl-2 transgene. Thus, NKAP is required for T cell maturation and the acquisition of functional competency.
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN, 55905, USA.
authors.forename: Fan-Chi
authors.initials: FC
authors.lastname: Hsu
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Pajerowski
authors.forename: Molly
authors.initials: M
authors.lastname: Nelson-Holte
authors.forename: Rhianna
authors.initials: R
authors.lastname: Sundsbak
authors.forename: Virginia Smith
authors.initials: VS
authors.lastname: Shapiro
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D002469:Cell Separation; D056970:Co-Repressor Proteins / Q000378:metabolism*; D005434:Flow Cytometry; D017353:Gene Deletion; D006801:Humans; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology; D019076:Transgenes
chemical_list: D056970:Co-Repressor Proteins; D053699:Interleukin-7 Receptor alpha Subunit; C479077:NKAP protein, human; C560431:NKAP protein, mouse; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins