The Role of CMV in Immunosenescence

Abstract

The term ``immunosenescence'' is commonly taken to mean age-associated changes in immune parameters hypothesized to contribute to increased susceptibility and severity of the older adult to infectious disease, autoimmunity and cancer. In humans, it is characterized by lower numbers and frequencies of naïve T and B cells and higher numbers and frequencies of late-differentiated T cells, especially CD8+ T cells, in the peripheral blood. The latter may be very noticeable, but intriguingly, only in people infected by human herpesvirus 5 (Cytomegalovirus, CMV). Almost all human studies have been cross-sectional, thus documenting differences between old and young populations, but not necessarily changes over time. Nonetheless, limited longitudinal studies have provided data consistent with gradually decreasing naïve T and B cells, and increasing late-differentiated T cells over time, and in rare instances associating these changes with increasing frailty and incipient mortality in the elderly. Low numbers of naïve cells render the aged highly susceptible to pathogens to which they have not been previously exposed, but are not otherwise associated with an ``immune risk profile'' predicting earlier mortality. Whether the accumulations of late-differentiated T cells driven primarily by CMV contribute to frailty and mortality or are only adaptive responses to the persistent virus remains controversial. Either way, there is currently little direct evidence that ``immunosenescence'' contributes to either autoimmunity or cancer in the aged. This chapter reviews some of the studies implicating CMV infection in immunosenescence and its consequences for ageing trajectories in humans.