Sara van den Berg

1 17 General introduction infection is not related to altered CD8 + T-cells dynamics in vivo , neither of the CMV-specific T-cells themselves, nor as an effect on other T-cell specificities. CD4 + memory T-cells in CMV+ individuals show an increased expression of late-stage differentiation markers and a trend towards lower T-cell production rates as compared to their counterparts in CMV- individuals. In chapter 7 , we had the unique opportunity to assess the effect of time since CMV infection in a 27-year longitudinal cohort. We address the contribution of duration of CMV infection on the immune system and general health. We asses CMV-specific antibody levels longitudinally and find that within individuals CMV-specific antibodies increase slightly over time. However, age is more strongly associated with CMV-specific antibody levels, regardless of duration of CMV infection. We also investigated whether T-cell ‘memory inflation’, i.e. an increase in CMV-specific T-cell numbers over time, occurs in humans. We find no convincing evidence for this process in humans. Older age at seroconversion is associated with increased CD4 + T-cell responses. Finally, we investigate if CMV infection and duration leads to adverse health outcomes in older adults. Interestingly, CMV-seropositivity and duration are not associated with adverse health, while higher age at CMV-seroconversion is. Our results suggest a model in which duration of CMV infection has less impact, and age at the moment of CMV seroconversion has more impact on the immune system than was previously appreciated. Chapter 8 summarizes the findings presented in this thesis and discusses them in a broader perspective.