Immunosenescence in humans : changes to the aged T Lymphocyte population in response to persistent Cytomegalovirus infection

Immunosenescence describes the decrease in immune function with advancing age, a phenomenon that is associated with changes in the B and T lymphocyte populations. CD8+ T cells display the most dramatic phenotypical and functional changes within the T cell compartment whereby the cohorts of effector and memory T cells expand while the total population and diversity of naive T cells both decline. The cause of immunosenescence is unknown; however, the accumulation of antigen-specific T cells, in particular cytomegalovirus (CMV)-specific T cells, may be a contributing factor. CMV is a beta human herpes virus that infects an extensive section of the global human population in which it may produce a lifelong, latent infection. This stimulates a highly immunogenic response that comprises a significant proportion of T cells that display a high specificity to CMV. It is postulated that this massive T cell inflation and subsequent exhaustion renders the T cell population senescent, reducing the immune system’s ability to combat pathogens as humans age. This review considers fundamental alterations in the immune system in the elderly, focusing on those changes within the CD8+ T cell population, and assesses the contribution of chronic CMV infection to immunosenescence. We propose that memory T cell inflation of CMV-infected individuals and ageing influence the functional and proliferative properties of human CMV-specific T cells, making them less efficient at controlling CMV reactivation.