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

Abstract

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. CMV seropositivity has also been linked to arterial stiffness and an increased risk of developing cardiovascular diseases (CVD). The RESIST Senior Individuals (SI) cohort is a population-based cohort with focus on the elderly, established to shed light on the age-related changes of the immune system and the accompanied reduced capability to fight infectious diseases. Here we investigated the frequency and phenotype of CMVpp65-specific CD8+ T cells in the circulation of individuals of different age groups by means of MHC-I tetramer staining and their associations with age and associated factors such as serostatus and blood pressure. In the SI cohort, the frequency of CMV-specific T cells within the CD8+ T cell fraction was increased with age, as previously reported. We add to previous knowledge by showing that this frequency is associated with the total percentage and absolute counts of CD8+ and CD4+CD8+ double-positive T cells within leukocytes. Systolic blood pressure (SBP) and history of CVD correlated with the frequency of CMV-specific CD8+ T cells. Focusing on CMV-specific T cell subtypes, we show here that the frequencies of TEM and CD27-expressing TEMRA cells were associated with higher age. TEM and CD27- TEMRA cell frequencies were increased in donors with high CMV-IgG titers. Furthermore, SBP significantly correlated with CMV-specific effector CD8+ T cells, which was mostly reflected by CD27- TEMRA cells. In conclusion, different effector T-cell subtypes were associated with age, serostatus and SBP, suggesting that it is not age per se that renders elderly CMV-positive individuals susceptible to CVD, but the immune response to CMV. Our study suggests that detailed immunophenotyping may identify individuals whose immune systems are strongly influenced by the response to CMV, leading to health consequences and impairing healthy aging.