Cytomegalovirus, CMV, is a prevalent form of herpesvirus, a persistent infection that cannot be effectively cleared by the immune system and continues to resurface over time following the initial exposure. Upwards of 90% of older people in the developed world have been exposed to CMV at some point in their lives. The immediate symptoms of CMV infection for most people are mild to non-existent, but there is reason to suspect that CMV acts over time to corrode the effectiveness of the adaptive immune system.
The adaptive immune system is a complex collection of many subpopulations of cells. One high-level view of the harm done by CMV is that its presence forces an expansion of the population of memory T cells dedicated to this one infectious agent at the expense of the myriad other duties that the T cell population should be undertaking. Any given category of T cells is not a monolith, however, is made up of many different T cell subtypes and behaviors, and the real picture is no doubt more complex than a simple expansion of one subtype.
Further, CMV most likely affects other portions of the immune system to a similar degree, and some of those influences may also be harmful over the long term, contributing to degenerative aging. In today's open access paper, researchers report on their investigation of the effects of CMV infection on immune cell populations that include innate immune cells known as monocytes. Monocytes and their descendant macrophages are involved in defense against pathogens, modulation of inflammatory signaling, tissue maintenance, and other duties. Note that the study is only comparing young versus old individuals with exposure to CMV, not uninfected individuals, however.
Markers of immunosenescence in CMV seropositive healthy elderly adults
A significant increase in life expectancy has accompanied the growth of the world's population. Approximately 10% of the global population are adults over 60, and it is estimated that 2050 this figure will double. This increase in the proportion of older adults leads to a more significant burden of age-related diseases. Immunosenescence predisposes elderly individuals to a higher incidence of infectious and chronic non-communicable diseases with higher mortality rates. Despite advances in research, it is necessary to evaluate the cellular characteristics of the aging immune system in populations with a high incidence of latent viruses such as cytomegalovirus (CMV). To that end, this study employed a group of 10 young people (18-28 years old with an average age of 24.5 ± 2.98 years, five men and five women) and a group of ten older adults (60-85 years old with a mean age of 67.9 ± 9.07 years, five men and five women).
Monocytes play a fundamental role in the immune response due to their phagocytic capacity, which is necessary for the processing and presentation of antigens and the production of cytokines. In aging, monocytes are critical cells in age-related immune dysfunction. Our study observed a decrease in classical CD14++CD16- monocytes and an increase in CD14+CD16+ intermediate monocytes in older adults. The intermediate monocytes are characterized as proinflammatory cells that produce cytokines such as TNFα and IL-6. These cytokines have been associated with chronic low-grade inflammation or inflammaging. Furthermore, previous studies have shown an association between variation in circulating monocyte subpopulations and the development of diseases such as coronary heart disease and various types of cancer.
When we analyzed natural killer (NK) cells in our sample, we observed a significant increase in CD56neg cells, increased expression of CD57, and a notable decrease in CD56bright cells in older adults. These findings align with previous immunosenescence research reporting a decrease in immature NK and an increase in CD56dim cells with CD57 expression. Studies have shown that CD56neg cells are less functional regarding cytotoxicity and responsiveness, especially in CMV+ individuals.
In this study, using the differential expression of CD62L and CD45RO, the distribution of memory subpopulations in the T cells was determined. A significant decrease in the naïve cell subpopulation was observed in CD4+ and CD8+ T cells in the older adult group. Although the total number of T cells remains relatively constant with aging, reducing the naïve T cells is a hallmark of immunosenescence. Furthermore, we observed a significant increase in terminally differentiated effector CD8+ T cells in older adults. This increase in T cell effectors has been observed in both aging and chronic infections, such as those caused by CMV, which is the case for our individuals.
View the full article at FightAging
