Is immunosenescence infectious?

Herpes viruses are endemic. Once established, the virus is never eliminated but persists throughout life. The fraction of infected individuals gradually increases with age, such that the majority of elderly people are cytomegalovirus (CMV)+, Epstein–Barr virus (EBV)+ and Varicella+. Clinically relevant reactivation of Varicella causes painful shingles; CMV reactivation can cause fatal pneumonia. Overt reactivation, even in the very elderly, occurs only in immunocompromised individuals; however, the necessity for maintaining immunity to these viruses is costly. We argue that this cost is not only reflected in the requirement for continuous immunosurveillance against these viruses but, more importantly, results in a re-configuration of T-cell immunity due to the accumulation of dysfunctional virus-specific cells, which fail to be eliminated from the system. Thus, we hypothesize that it is the chronic antigenic stimulation by CMV (and possibly other persisting antigens) that leads to an increasing prevalence of senescent, dysfunctional T cells, and therefore contributes to more general alterations in the immune system, which are associated with earlier mortality.