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Description
The elderly population is particularly susceptible to infectious diseases, such as influenza, as evidenced by increased occurrence and severity of infection, and reduced vaccine efficacy. Studies suggest an association between persistent cytomegalovirus (CMV) infection and deficiencies of the aged immune system. CMV is a common herpes virus that infects up to 85% of the population aged 40 years or over. Healthy individuals rarely experience symptoms after the initial CMV infection. However, the virus remains in the body in an inactive state and constant surveillance by the immune system is required to detect and suppress reactivation of the virus. It is unclear whether this lifelong burden on the immune system to control persistent CMV infection plays a causal role in age-related compromise of the immune system to fight infections and respond to vaccines.
The effect of age on the immune system is multifactorial. One factor is a decline in the diversity of CD8+ “killer” T cells recruited by the immune system to fight a particular infection. In this study we investigated whether the presence of lifelong CMV infection impacts the diversity of T cells responding to another infection in aged mice. The diversity of T cells responding to infection was assessed using single-cell Sanger sequencing and bioinformatics analysis of the T cell receptors, which are expressed on the surface of individual T cells to enable the detection of virus. Various features of the T cell receptors, including diversity, gene usage, sequence length, and conserved patterns of amino acid usage were quantitatively compared between three groups of mice: young adult and old adult mice with no CMV infection and old mice with lifelong CMV infection. T cell diversity was quantified using ecological measures of diversity and rarefaction to standardize for differences in sample sizes. Our results demonstrate that, in the absence of persistent CMV infection, T cell responses in old mice were significantly less diverse than in young adult mice. In contrast, T cell diversity was maintained in the old mice with CMV infection and we did not observe the age-related narrowing of the T cell population that occurred in the absence of persistent CMV infection. Next-generation sequencing of the broader T cell populations that have not previously encountered infection showed similar T cell diversity in all three groups of mice, including the presence of T cell receptors that were recruited into the immune response in CMV-infected old mice but not in old mice without CMV infection.
These results suggest that lifelong CMV infection may actually improve T cell immunity in later life by broadening the diversity of T cells that can be effectively recruited and/or maintained in immune responses to other infections. Furthermore, these results challenge the paradigm that CMV has a negative impact on the ageing immune system.
