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Updated: Jun 9, 2026

A DNA/Ki67-Based Flow Cytometry Assay for Cell Cycle Analysis of Antigen-Specific CD8 T Cells in Vaccinated Mice
Published on: January 5, 2021
Regulation of memory CD8 T-cell differentiation by cyclin-dependent kinase inhibitor p27Kip1
Anju Singh1, Anna Jatzek, Erin Hemmila Plisch
1Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
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.
Insights
The cyclin-dependent kinase inhibitor p27(Kip1) regulates CD8 T-cell memory formation. Removing p27(Kip1) enhances T-cell memory and recall responses, improving vaccine efficacy.
Area of Science:
- Immunology
- Cell Biology
- Vaccinology
Background:
- T-cell memory is crucial for effective vaccination.
- Molecular mechanisms controlling CD8 T-cell memory formation are not fully understood.
- Cell cycle regulation of CD8 T-cell proliferation and survival during immune responses is poorly defined.
Purpose of the Study:
- To identify molecular regulators of CD8 T-cell homeostasis and memory formation.
- To investigate the role of cell cycle regulators in CD8 T-cell responses to viral infection.
- To determine the impact of p27(Kip1) on T-cell memory magnitude and quality.
Main Methods:
- Studied CD8 T-cell responses in mice during acute viral infection.
- Utilized genetic models to investigate the function of p27(Kip1).
- Assessed T-cell proliferation, apoptosis, and memory recall responses.
Main Results:
- Identified p27(Kip1) as a critical regulator of CD8 T-cell homeostasis.
- p27(Kip1) acts as a timer for cell cycle exit, limiting memory precursor expansion.
- Absence of p27(Kip1) resulted in enhanced CD8 T-cell memory and recall responses, particularly effector memory cells.
Conclusions:
- p27(Kip1) critically controls CD8 T-cell homeostasis and memory formation.
- Modulating p27(Kip1) can enhance vaccine-induced T-cell memory and protective immunity.
- Findings provide insights into cell cycle regulation of T-cell memory.
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