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Updated: May 25, 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
Defective CD8 T cell responses in aged mice are due to quantitative and qualitative changes in virus-specific
Vilma Decman1, Brian J Laidlaw, Travis A Doering
1Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Abstract:
Aging is associated with suboptimal CD8 T cell responses to viral infections. It is not clear whether these poor responses are due to environmental influences or quantitative and qualitative changes in the pool of responding CD8 T cells. Our studies demonstrated several deleterious age-related changes in the pool of Ag-specific CD8 T cells that respond to infection. The majority of CD8 T cells from uninfected aged mice was CD44(Hi) and had increased expression of inhibitory receptors including PD1, LAG3, 2B4, and CD160. These aged CD44(Hi) CD8 T cells were transcriptionally similar to exhausted CD8 T cells found during chronic infections. In addition, the number of virus-specific precursors in aged mice prior to infection was decreased up to 10-fold, and many of these Ag-specific precursors had high expression of CD44 and PD1. Finally, TCR transgenic studies demonstrated that the CD44(Hi) Ag-specific CD8 T cells from unimmunized aged and young mice were qualitatively inferior compared with CD44(Lo) CD8 T cells from aged or young donors. Thus, a decrease in precursor frequency as well as qualitative changes of CD8 T cells during aging are directly related to impaired immunity.
Insights
Aging impairs CD8 T cell immunity due to fewer virus-specific precursors and lower quality T cells. Aged CD8 T cells exhibit exhaustion markers, reducing immune response effectiveness against infections.
Area of Science:
- Immunology
- Aging Research
- Infectious Disease
Background:
- Aging is linked to diminished CD8 T cell responses during viral infections.
- The causes of these suboptimal responses remain unclear, with possibilities including environmental factors or intrinsic changes in T cells.
Purpose of the Study:
- To investigate age-related quantitative and qualitative changes in antigen-specific CD8 T cells.
- To determine the impact of these changes on immune response to viral infections.
Main Methods:
- Analysis of CD8 T cell populations in aged and young mice, focusing on CD44 expression and inhibitory receptors (PD1, LAG3, 2B4, CD160).
- Transcriptional profiling of aged CD8 T cells.
- Assessment of virus-specific precursor frequencies.
- T cell receptor (TCR) transgenic studies to compare CD44(Hi) and CD44(Lo) CD8 T cell function.
Main Results:
- Aged mice showed a majority of CD8 T cells with high CD44 expression and increased inhibitory receptors, resembling exhausted T cells.
- Virus-specific CD8 T cell precursors decreased significantly (up to 10-fold) in aged mice, with many exhibiting high CD44 and PD1 expression.
- CD44(Hi) CD8 T cells from aged mice were qualitatively inferior to CD44(Lo) cells, irrespective of donor age.
Conclusions:
- Aging leads to a reduced number of virus-specific CD8 T cell precursors.
- Qualitative defects in CD8 T cells, characterized by increased exhaustion markers and impaired function, contribute to decreased immunity in aged individuals.
- Both decreased precursor frequency and altered T cell quality are directly implicated in impaired immune responses during aging.
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