Aging and CMV discordance are associated with increased immune diversity between monozygotic twins

Abstract

Background Broadly, much of variance in immune system phenotype has been linked to the influence of non-heritable factors rather than genetics. In particular, two non-heritable factors: aging and human cytolomegavirus (CMV) infection, have been known to account for significant inter-individual immune variance. However, many specific relationships between them and immune composition remain unclear, especially between individuals over narrower age ranges. Further exploration of these relationships may be useful for informing personalized intervention development. Results To address this need, we evaluated 41 different cell type frequencies by mass cytometry and identified their relationships with aging and CMV seropositivity. Analyses were done using 60 healthy individuals, including 23 monozygotic twin pairs, categorized into young (12–31 years) and middle-aged (42–59 years). Aging and CMV discordance were associated with increased immune diversity between monozygotic twins overall, and particularly strongly in various T cell populations. Notably, we identified 17 and 11 cell subset frequencies as relatively influenced and uninfluenced by non-heritable factors, respectively, with results that largely matched those from studies on older-aged cohorts. Next, CD4+ T cell frequency was shown to diverge with age in twins, but with lower slope than in demographically similar non-twins, suggesting that much inter-individual variance in this cell type can be attributed to interactions between genetic and environmental factors. Several cell frequencies previously associated with memory inflation, such as CD27- CD8+ T cells and CD161+ CD4+ T cells, were positively correlated with CMV seropositivity, supporting findings that CMV infection may incur rapid aging of the immune system. Conclusions Our study confirms previous findings that aging, even within a relatively small age range and by mid-adulthood, and CMV seropositivity, both contribute significantly to inter-individual immune diversity. Notably, we identify several key immune cell subsets that vary considerably with aging, as well as others associated with memory inflation which correlate with CMV seropositivity.

Association of Premature Immune Aging and Cytomegalovirus After Solid Organ Transplant

“…The unbiased analysis also identified changing populations of both CD4 T cells and NK cells, which could also be of interest for further study. CMV and aging are both known to promote variation across immune cell types between individuals ( 62 ), and studying these populations will be important to understanding the impact of this variation after transplantation.…”

Comparison of Humoral and Cellular CMV Immunity in Patients Awaiting Kidney Transplantation

“…Previous studies indicate that age significantly affects an individual’s immune response toward CMV [ 26 , 28 , 29 ]. The current study could confirm these findings, when performing multivariate analysis.…”

Asymptomatic or mild symptomatic SARS-CoV-2 infection elicits durable neutralizing antibody responses in children and adolescents

“…Notably, SARS-CoV-2 infection in children and adolescents is often asymptomatic or associated with such minor symptoms that children infrequently come to medical attention (9,10). The varied clinical manifestations of SARS-CoV-2 infection among children and adults suggest that age may modify the host response to SARS-CoV-2, as has previously been demonstrated for several other viruses (11)(12)(13)(14)(15)(16)(17). To date, studies of SARS-CoV-2 immune responses in pediatric populations have focused primarily on children hospitalized for severe COVID-19 or who developed multisystem inflammatory syndrome in children (MIS-C), a potentially life-threatening inflammatory condition that can occur after SARS-CoV-2 infection (18)(19)(20)(21)(22).…”