title: Latent infection with cytomegalovirus is associated with poor memory CD4 responses to influenza A core proteins in the elderly.
abstract: Influenza remains a major pathogen in older people. Infection with CMV and the accumulation of late-differentiated T cells associated with it have been implicated in poor Ab responsiveness to influenza vaccination in the elderly, most of whom are CMV positive. However, whether CMV infection also affects memory T cell responses to influenza remains unknown. To investigate this, we assessed T cell responses to influenza A matrix protein and nucleoprotein ex vivo in 166 Dutch individuals (mean age 62.2 y, range 42-82) and validated the results in a second cohort from North America (mean age 73.1 y, range 65-81, n = 28). We found that less than half of the CMV-infected older subjects mounted a CD4 T cell response to influenza Ags, whereas ∼80% of uninfected elderly did so. A similar proportion of younger subjects possessed influenza A virus-responsive CD4 T cells, and, interestingly, this was the case whether they were CMV-infected. Thus, the effect of CMV was only seen in the older donors, who may have been exposed to the virus for decades. The percentage of donors with CD8 responses to influenza A virus was lower than those with CD4; this was not influenced by whether the subjects were CMV seropositive or seronegative. CMV-seropositive responders had significantly higher frequencies of late-differentiated CD4 T-cells (CD45RA(+/-)CCR7(-)CD27(-)CD28(-)) compared with CMV-infected nonresponders. These data add to the accumulating evidence that infection with CMV has profound but heterogeneous effects on responses to the products of other viruses and have implications for the design of influenza vaccines, especially in the elderly.
authors.affiliation: Department of Internal Medicine II, Centre for Medical Research, University of Tubingen, 72072 Tubingen, Germany; Evelyna.Derhovanessian@biontech.de.
authors.forename: Evelyna
authors.initials: E
authors.lastname: Derhovanessian
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Centre, 2333 ZC Leiden, the Netherlands; Netherlands Consortium for Health Aging, Leiden University Medical Centre, 2333 ZC Leiden, the Netherlands; Department of Internal Medicine, Section of Gerontology and Geriatrics, VU University Medical Centre, 1081 HV Amsterdam, the Netherlands;
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Maier
authors.affiliation: Department of Internal Medicine II, Centre for Medical Research, University of Tubingen, 72072 Tubingen, Germany;
authors.forename: Karin
authors.initials: K
authors.lastname: Hähnel
authors.affiliation: Advanced Medical Research Institute of Canada, Sudbury, Ontario, Canada P3E 5J1; and.
authors.forename: Janet E
authors.initials: JE
authors.lastname: McElhaney
authors.affiliation: Netherlands Consortium for Health Aging, Leiden University Medical Centre, 2333 ZC Leiden, the Netherlands; Section of Molecular Epidemiology, Leiden University Medical Centre, Leiden, the Netherlands.
authors.forename: Eline P
authors.initials: EP
authors.lastname: Slagboom
authors.affiliation: Department of Internal Medicine II, Centre for Medical Research, University of Tubingen, 72072 Tubingen, Germany;
authors.forename: Graham
authors.initials: G
authors.lastname: Pawelec
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology; D008297:Male; D008875:Middle Aged; D014758:Viral Core Proteins / Q000276:immunology*; D017735:Virus Latency / Q000276:immunology*
chemical_list: D007252:Influenza Vaccines; D014758:Viral Core Proteins