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IFNγ⁻TNFα⁻IL2⁻MIP1α⁻CD107a⁺PRF1⁺ CD8 pp65-Specific T-Cell Response Is Independently Associated With Time to Death in
Sara Ferrando-Martínez1, Ezequiel Ruiz-Mateos2, Joseph P Casazza3
1Laboratorio de InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain. Laboratory of Immunovirology, Clinic Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, IBiS, Virgen del Rocío University Hospital, Sevilla, Spain.
Abstract:
Persistent cytomegalovirus (CMV) infection has been suggested to be a major driving force in the immune deterioration and an underlying source of age-related diseases in the elderly. CMV antibody titers are associated with lower responses to vaccination, cardiovascular diseases, frailty, and mortality. CMV infection is also associated with shorter T-cell telomeres and replicative senescence. Although an age-related deregulation of CMV-specific T-cell responses could be an underlying cause of the relationship between CMV and immune defects, strong and polyfunctional responses are observed in elderly individuals, casting uncertainty on their direct role in age-related immune frailty. In this study, we longitudinally followed a cohort of healthy donors aged over 50 years, assessing their mortality rates and time to death during a 2-year period. Specific T-cell responses to the immunodominant antigen pp65 (IFNγ, TNFα, IL2, MIP1α, CD107a, and perforin production) were analyzed at the beginning of the 2-year observation period. A cytotoxic CD8 pp65-specific T-cell response, without cytokine or chemokine coexpression, was independently associated with all-cause mortality in these elderly individuals. This pp65-specific CD8 T-cell response could be a useful tool to identify individuals with depressed immune function and a higher risk of death.
Insights
Persistent cytomegalovirus (CMV) infection is linked to aging immune systems. A specific cytotoxic CD8 T-cell response to pp65 antigen predicts mortality risk in older adults.
Area of Science:
- Immunology
- Gerontology
- Infectious Diseases
Background:
- Persistent cytomegalovirus (CMV) infection is implicated in age-related immune decline and associated diseases.
- CMV antibody titers correlate with adverse health outcomes including frailty and mortality.
- The role of CMV-specific T-cell responses in age-related immune dysfunction remains unclear.
Purpose of the Study:
- To investigate the association between CMV-specific T-cell responses and mortality in healthy elderly individuals.
- To identify potential immune biomarkers for predicting mortality risk in aging populations.
Main Methods:
- Longitudinal cohort study of healthy donors over 50 years old.
- Assessment of mortality rates over a 2-year period.
- Analysis of specific T-cell responses to CMV pp65 antigen (cytokine production, CD107a, perforin).
Main Results:
- A cytotoxic CD8 T-cell response targeting pp65, lacking cytokine coexpression, was independently associated with all-cause mortality.
- This specific T-cell response profile was observed in elderly individuals.
- The findings suggest a link between a particular type of CMV immune response and increased mortality risk.
Conclusions:
- A specific cytotoxic CD8 pp65-specific T-cell response may serve as a biomarker for identifying elderly individuals at higher risk of death.
- This response could indicate depressed immune function in the context of aging.
- Further research is warranted to explore the mechanisms underlying this association.
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