TY - JOUR
T1 - NKAP is required for T cell maturation and acquisition of functional competency
AU - Hsu, Fan Chi
AU - Pajerowski, Anthony G.
AU - Nelson-Holte, Molly
AU - Sundsbak, Rhianna
AU - Shapiro, Virginia Smith
PY - 2011/6
Y1 - 2011/6
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20101874
DO - 10.1084/jem.20101874
M3 - Article
C2 - 21624937
AN - SCOPUS:79958290116
SN - 0022-1007
VL - 208
SP - 1291
EP - 1304
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 6
ER -