The Polyfunctionality of Human Memory CD8+ T Cells Elicited by Acute and Chronic Virus Infections Is Not Influenced by Age

PLoS Pathogens

Mario Ventresca¹  Michael R. Betts²  Robin Parsons³  Carole Evelegh³  Dawn Bowdish³  Jonathan L. Bramson³  Alina Lelic³  Mark B. Loeb³  Chris P. Verschoor³ 

[1] Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Ontario, Canada;Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States;McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada

关键词: T cells;    Cytotoxic T cells;    West Nile virus;    Memory T cells;    Cytokines;    Principal component analysis;    Elderly;    Immune response;   

DOI  :  10.1371/journal.ppat.1003076

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

As humans age, they experience a progressive loss of thymic function and a corresponding shift in the makeup of the circulating CD8+ T cell population from naïve to memory phenotype. These alterations are believed to result in impaired CD8+ T cell responses in older individuals; however, evidence that these global changes impact virus-specific CD8+ T cell immunity in the elderly is lacking. To gain further insight into the functionality of virus-specific CD8+ T cells in older individuals, we interrogated a cohort of individuals who were acutely infected with West Nile virus (WNV) and chronically infected with Epstein Barr virus (EBV) and Cytomegalovirus (CMV). The cohort was stratified into young (<40 yrs), middle-aged (41–59 yrs) and aged (>60 yrs) groups. In the aged cohort, the CD8+ T cell compartment displayed a marked reduction in the frequency of naïve CD8+ T cells and increased frequencies of CD8+ T cells that expressed CD57 and lacked CD28, as previously described. However, we did not observe an influence of age on either the frequency of virus-specific CD8+ T cells within the circulating pool nor their functionality (based on the production of IFNγ, TNFα, IL2, Granzyme B, Perforin and mobilization of CD107a). We did note that CD8+ T cells specific for WNV, CMV or EBV displayed distinct functional profiles, but these differences were unrelated to age. Collectively, these data fail to support the hypothesis that immunosenescence leads to defective CD8+ T cell immunity and suggest that it should be possible to develop CD8+ T cell vaccines to protect aged individuals from infections with novel emerging viruses.

【 授权许可】

CC BY