Sara van den Berg

89 4 CMV on influenza infection ABSTRACT Latent infection with cytomegalovirus (CMV) is thought to contribute to the age-associated decline of the immune system. CMV induces large changes in the T-cell pool and may thereby affect other immune responses. This is thought to impact especially older adults, who are at higher risk of hospitalization and death upon influenza virus infection. Here, we investigated the impact of age and CMV infection on influenza virus-specific T-cell frequencies in healthy individuals (n=96), as well as the response to influenza virus infection in older adults (n=72). We assessed two major hypotheses of CMV-enhanced ageing: 1) impairment of the immune response due to the presence of large CMV-specific clonal expansions filling the ‘immunological space’, and 2) reduced immune responses as a result of a lingering low- graded level of inflammation by CMV. We found that influenza virus-specific T-cell frequencies were decreased in healthy CMV+ older adults versus CMV- older adults. However, specific T-cell responses upon acute influenza virus infection were not negatively affected by CMV infection. We found no evidence for filling immunological space, as there was no negative association between influenza virus- specific T-cell frequencies, phenotype, or IFN γ responses with CMV-serostatus, CMV-specific antibody levels, or CMV-specific T-cell responses at any time point. We found no association between CMV infection and inflammatory cytokine levels in serum during influenza virus infection. Inflammatory cytokine levels were also not associated with the height of the influenza virus-specific T-cell response upon infection. Finally, CMV infection was not associated with increased severity of influenza-related symptoms. In fact, CMV infection was even associated with increased influenza virus-specific T-cell responses upon influenza virus infection. In conclusion, although associated with lower frequencies of influenza virus- specific memory T-cells in healthy individuals, CMV infection does not seem to form a threat for a proper T-cell response during acute influenza virus infection in older adults.