Journal
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
Volume 70, Issue 10, Pages 1210-1218Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/gerona/glu171
Keywords
CMV-specific T-cell response; CMV; Aging; Mortality; Perforin
Categories
Funding
- Fondo de Investigaciones Sanitarias [CD10/00382, CP08/00172]
- Proyecto de Excelencia [CTS-6313]
- RETIC program
- Redes Tematicas de Investigacion en SIDA [ISCIII RETIC RD12/0017/0029, RD12/0017/0037]
- Consejeria de Salud [PI-0278]
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
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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 (IFN gamma, TNF alpha, IL2, MIP1 alpha, 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.
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