Cytomegalovirus in the Immunology of Aging
The open access editorial noted here serves as an introduction to some of the current thinking on the role of cytomegalovirus (CMV) in the age-related decline of the immune system. CMV infection is pervasive throughout the population, particularly in the old. This persistent viral infection cannot be effectively cleared by the immune system, and an ever greater percentage of immune cells become uselessly specialized to fight CMV. This leaves ever fewer immune cells ready to tackle other threats. This seems an important component of immune dysfunction, one that can perhaps be addressed by selectively destroying these immune cells to free up space for replacements. The research community is by no means unified on this view of CMV, however, as illustrated here.
Aging represents a paradox of immunodeficiency and inflammation (inflammaging) and autoimmunity. Over the lifespan there are changes in the architecture and functioning of the immune system, often termed immunosenescence. Recently, there have been major developments in understanding the cellular and molecular bases, and genetic and epigenetic changes, in the innate and the adaptive immune system during aging, and the interactions between these separate arms of vertebrate immunity. Limited longitudinal studies have begun to reveal biomarkers of immune aging, which may be considered to constitute an "immune risk profile" (IRP) predicting mortality and frailty in the very elderly. Hallmark parameters of the IRP may also be associated with poorer responses to vaccination.
The usually asymptomatic infection with the widespread persistent cytomegalovirus, CMV, has an enormous impact on immune biomarkers, but according to the circumstances and depending on what is measured, this can translate into a detrimental or a beneficial effect. The prevalence of CMV infection in populations in industrialized countries increases with age, and within individuals the degree of immune commitment to anti-CMV responses also increases with age. This may cause pathology by maintaining higher systemic levels of inflammatory mediators ("inflammaging") and decreasing the "immunological space" available for immune cells with other specificities, or it may exert beneficial "adjuvant-like" effects. Modalities to prevent or reverse immunosenescence may therefore need to include targeting infectious agents such as CMV in a robustly personalized manner.
Because of the increasing recognition that CMV has a marked impact on immune parameters commonly associated with age, it is crucial to dissect out whether age or CMV is responsible for altering biomarkers predictive of health status (e.g., frailty) or other important parameters such as response to vaccination (especially seasonal influenza). Researchers have investigated whether T cell responsiveness to a range of CMV proteins is different in younger and older healthy people and whether relaxation of anti-CMV immunosurveillance in later life could contribute to disease. They found that CMV-specific CD4+ T cells secreting the anti-inflammatory cytokine IL 10 were predominantly directed to latency-associated CMV proteins and that these responses were not greater in the elderly than the young. However, the frequency of IFN-γ-secreting CD4+ T cells correlated with latent viral genome copy number in monocytes. They conclude that viremia is rare in the elderly due to the maintenance of T cell responsiveness but that CMV can be an important comorbidity factor in people who are not perfectly healthy.
Further complications in analyzing the impact of CMV may arise because most human data are derived from studies using peripheral blood. However, the bone marrow harbors large amounts of late-stage differentiated CD8 T cells possibly because the production of IL 15 is greater in CMV-infected individuals. Also, expression of the NK-associated receptor CD161 is similar in CMV-seropositive and seronegative young subjects but is different in the elderly, illustrating that CMV effects may be different at different ages. The large accumulations of CMV-specific T cells, also in the bone marrow, may contribute to the state of inflammaging, but it is likely that other immune (and non-immune) cells are also major contributors. Cells of the innate immune system far outnumber those of adaptive immunity and may also be heavily influenced by the presence of CMV, contributing to inflammaging.
I found out at my last blood donation that I don't have CMV. Unfortunately I did have chicken pox when I was a kid, so I guess I'm still in the same boat?