Cytomegalovirus and immune senescence: Culprit or innocent bystander?

Immune senescence may be defined as the age-related reduction and dysregulation of immune function, and has been associated with increased incidence and severity of infectious diseases and with poor efficacy of prophylactic vaccines in the elderly. Several studies have demonstrated that persistent infections with Herpes viruses in general and Cytomegalovirus (CMV) in particular have a profound influence on subset distribution, phenotype and potentially also on the function of T cells in ageing individuals. The association of CMV-seropositivity and accumulation of CMV-specific CD8+ T cells with decreased survival in longitudinal studies of very elderly has fostered the hypothesis that CMV-infection may be an important causative factor for the development of immune senescence. Here, we have critically summarized the current body of evidence supporting this hypothesis, highlight some controversial issues about its relevance and mechanisms and propose areas of future research to demonstrate unequivocally whether and how persistent infections might compromise the ageing immune system.