Different CMV-specific effector T cell subtypes are associated with age, CMV serostatus, and increased systolic blood...

Cytomegalovirus (CMV) infection is one of the most common infections in humans, and CMV antigens are the major drivers of repetitive T-cell stimulation as a part of a well-adapted immune response in immunocompetent individuals. With higher age, the recurrent clonal expansion of CMV-specific T cells results in high frequencies of CMV-specific effector T cells. Further on, CMV seropositivity has been linked to an increased risk of developing cardiovascular diseases (CVD). Here we investigated the frequency and phenotype of CMV-specific T cells in the circulation of a population cohort of 650 individuals focusing on the age group over 60 years. Circulating immune cells of individuals carrying the HLA-A*02 allele were investigated (n = 302) applying MHC class I tetramers.

We add to previous knowledge by showing that the frequency of CMVpp65-specific CD8⁺ T cells is associated with the total percentage and absolute counts of CD8⁺ and CD4⁺CD8⁺ double-positive T cells within leukocytes, and further with systolic blood pressure (SBP) and history of CVD. An investigation into the differentiation status of CMV-specific T cells revealed an association of higher age and increased frequencies of both T_EM and CD27-expressing T_EMRA cells. In contrast, higher CMV-IgG titers were found to be associated with T_EM and CD27^- T_EMRA cell frequencies. SBP significantly correlated with CMV-specific effector CD8⁺ T cells, which was mostly reflected by CD27^- T_EMRA cells.

Within the circulating CMV-specific T cell population, different effector T-cell subtypes were associated with age, serostatus and SBP. This suggests that it is not age or infection per se that render CMV-positive individuals susceptible to CVD, but rather the cellular immune response to CMV. Detailed immunophenotyping may identify individuals whose immune systems are strongly influenced by the response to CMV, leading to health consequences and impairing healthy aging.