NKAP is required for T cell maturation and acquisition of functional competency

Fan Chi Hsu, Anthony G. Pajerowski, Molly Nelson-Holte, Rhianna Sundsbak, Virginia Smith Shapiro

Research output: Contribution to journalArticle

38 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1291-1304
Number of pages14
JournalJournal of Experimental Medicine
Volume208
Issue number6
DOIs
StatePublished - Jun 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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