title: Cytotoxic polyfunctionality maturation of cytomegalovirus-pp65-specific CD4 + and CD8 + T-cell responses in older adults positively correlates with response size.
abstract: Cytomegalovirus (CMV) infection is one of the most common persistent viral infections in humans worldwide and is epidemiologically associated with many adverse health consequences during aging. Previous studies yielded conflicting results regarding whether large, CMV-specific T-cell expansions maintain their function during human aging. In the current study, we examined the in vitro CMV-pp65-reactive T-cell response by comprehensively studying five effector functions (i.e., interleukin-2, tumor necrosis factor-α, interferon-γ, perforin, and CD107a expression) in 76 seropositive individuals aged 70 years or older. Two data-driven, polyfunctionality panels (IL-2-associated and cytotoxicity-associated) derived from effector function co-expression patterns were used to analyze the results. We found that, CMV-pp65-reactive CD8 + and CD4 + T cells contained similar polyfunctional subsets, and the level of polyfunctionality was related to the size of antigen-specific response. In both CD8 + and CD4 + cells, polyfunctional cells with high cytotoxic potential accounted for a larger proportion of the total response as the total response size increased. Notably, a higher serum CMV-IgG level was positively associated with a larger T-cell response size and a higher level of cytotoxic polyfunctionality. These findings indicate that CMV-pp65-specific CD4 + and CD8 + T cell undergo simultaneous cytotoxic polyfunctionality maturation during aging.
authors.affiliation: Institute of Cell Engineering, Johns Hopkins School of Medicine, USA.|Department of Medicine and Nephrology, Far Eastern Memorial Hospital, Taiwan.|Graduate Program of Biomedical Informatics, Yuan Ze University College of Informatics, Taiwan.
authors.forename: Yen-Ling
authors.initials: YL
authors.lastname: Chiu
authors.affiliation: Division of General Medicine and Geriatric Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taiwan.
authors.forename: Chung-Hao
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Institute of Cell Engineering, Johns Hopkins School of Medicine, USA.|Department of Microbiology and Immunology, National Defense Medical Center, Taiwan.
authors.forename: Bo-Yi
authors.initials: BY
authors.lastname: Sung
authors.affiliation: Department of Epidemiology, National Yang Ming University School of Public Health, Taiwan.
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Chuang
authors.affiliation: Institute of Cell Engineering, Johns Hopkins School of Medicine, USA.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Schneck
authors.affiliation: Division of Medicine, Pathogen Host Interaction, Brighton and Sussex Medical School, United Kingdom.
authors.forename: Florian
authors.initials: F
authors.lastname: Kern
authors.affiliation: Department of Internal Medicine II, University of Tubingen Center for Medical Research, Germany.
authors.forename: Graham
authors.initials: G
authors.lastname: Pawelec
authors.affiliation: Division of Geriatric Medicine and Gerontology, Biology of Healthy Aging Program, Johns Hopkins University School of Medicine, USA.
authors.forename: George C
authors.initials: GC
authors.lastname: Wang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology* / Q000472:pathogenicity; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D008297:Male; D010750:Phosphoproteins / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha; D014763:Viral Matrix Proteins / Q000276:immunology*
chemical_list: D010750:Phosphoproteins; D014409:Tumor Necrosis Factor-alpha; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa