Dataset Information


Regulation of memory CD8 T-cell differentiation by cyclin-dependent kinase inhibitor p27Kip1.

ABSTRACT: Induction of potent T-cell memory is the goal of vaccinations, but the molecular mechanisms that regulate the formation of memory CD8 T cells are not well understood. Despite the recognition that controls of cellular proliferation and apoptosis govern the number of memory T cells, the cell cycle regulatory mechanisms that control these key cellular processes in CD8 T cells during an immune response are poorly defined. Here, we have identified the cyclin-dependent kinase inhibitor p27(Kip1) as a critical regulator of the CD8 T-cell homeostasis at all phases of the T-cell response to an acute viral infection in mice. By acting as a timer for cell cycle exit, p27(Kip1) curtailed the programmed expansion of interleukin-2-producing memory precursors and markedly limited the magnitude and quality of CD8 T-cell memory. In the absence of p27(Kip1), CD8 T cells showed superior recall responses shortly after vaccination with recombinant Listeria monocytogenes. Additionally, we show that p27(Kip1) constrains proliferative renewal of memory CD8 T cells, especially of the effector memory subset. These findings provide critical insights into the cell cycle regulation of CD8 T-cell homeostasis and suggest that modulation of p27(Kip1) could bolster vaccine-induced T-cell memory and protective immunity.


PROVIDER: S-EPMC2953046 | BioStudies | 2010-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2013-01-01 | S-EPMC3570738 | BioStudies
2011-01-01 | S-EPMC3160490 | BioStudies
1000-01-01 | S-EPMC5943672 | BioStudies
1000-01-01 | S-EPMC4653222 | BioStudies
1000-01-01 | S-EPMC1636809 | BioStudies
2013-01-01 | S-EPMC3622674 | BioStudies
1000-01-01 | S-EPMC2941332 | BioStudies
2009-01-01 | S-EPMC2680713 | BioStudies
2000-01-01 | S-EPMC18275 | BioStudies
1000-01-01 | S-EPMC2663293 | BioStudies