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Aging and cytomegalovirus infection differentially and jointly affect distinct circulating T cell subsets in humans
Anne M Wertheimer1, Michael S Bennett, Byung Park
1Arizona Center on Aging, University of Arizona College of Medicine, Tucson, AZ 85724;
Abstract:
The impact of intrinsic aging upon human peripheral blood T cell subsets remains incompletely quantified and understood. This impact must be distinguished from the influence of latent persistent microorganisms, particularly CMV, which has been associated with age-related changes in the T cell pool. In a cross-sectional cohort of 152 CMV-negative individuals, aged 21-101 y, we found that aging correlated strictly to an absolute loss of naive CD8, but not CD4, T cells but, contrary to many reports, did not lead to an increase in memory T cell numbers. The loss of naive CD8 T cells was not altered by CMV in 239 subjects (range 21-96 y), but the decline in CD4(+) naive cells showed significance in CMV(+) individuals. These individuals also exhibited an absolute increase in the effector/effector memory CD4(+) and CD8(+) cells with age. That increase was seen mainly, if not exclusively, in older subjects with elevated anti-CMV Ab titers, suggesting that efficacy of viral control over time may determine the magnitude of CMV impact upon T cell memory, and perhaps upon immune defense. These findings provide important new insights into the age-related changes in the peripheral blood pool of older adults, demonstrating that aging and CMV exert both distinct and joint influence upon blood T cell homeostasis in humans.
Insights
Aging causes a loss of naive CD8 T cells, but not CD4 T cells, in humans. Cytomegalovirus (CMV) impacts CD4 naive cell decline and increases memory T cells in older adults.
Area of Science:
- Immunology
- Gerontology
- Virology
Background:
- Intrinsic aging affects human peripheral blood T cell subsets.
- Distinguishing aging's impact from persistent microorganisms like Cytomegalovirus (CMV) is crucial.
- CMV is linked to age-related T cell pool alterations.
Purpose of the Study:
- To quantify the impact of intrinsic aging on T cell subsets.
- To differentiate aging effects from CMV influence on T cells.
- To investigate the combined effects of aging and CMV on T cell homeostasis.
Main Methods:
- Cross-sectional study of 152 CMV-negative individuals (aged 21-101 years).
- Analysis of T cell subsets (CD4, CD8, naive, memory, effector/effector memory).
- Comparison between CMV-negative and CMV-positive subjects (n=239, aged 21-96 years).
Main Results:
- Aging correlated with absolute loss of naive CD8 T cells, independent of CMV.
- Aging did not increase memory T cell numbers in CMV-negative individuals.
- CMV presence significantly accelerated CD4 naive T cell decline and increased effector/effector memory T cells with age, particularly in those with high anti-CMV antibody titers.
Conclusions:
- Aging distinctly reduces naive CD8 T cells.
- CMV and aging have joint effects on T cell homeostasis, influencing naive CD4 T cell decline and memory cell expansion.
- Viral control efficacy may modulate CMV's impact on T cell memory and immune defense in aging individuals.
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