The inverted CD4:CD8 ratio is associated with cytomegalovirus, poor cognitive and functional states in older adults

Some premature features of immunosenescence have been associated with persistent viral infections and altered populations of T cells. In particular, the inverted T CD4:CD8 ratio has been correlated with increased morbidity and mortality across different age groups.

Here, we investigated the role of persistent viral infections, cognitive and functional states as predictors of inverted CD4:CD8 ratio of older adults in a developing country.

Three hundred and sixty community-dwelling older adults (aged 60-103 years) were recruited. Cognitive function was evaluated by the Instrument of Brief Neuropsychological Assessment and Mini-Mental State Examination inventory. Functional Activities Questionnaire was used to determine activities of daily living. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) serologies were determined by ELISAs. Peripheral blood was assessed for lymphocyte subsets by flow cytometry (CD4+, CD8+, NK, NKT, B and CD8+CD28-).

Fifty-nine individuals were identified with CD4:CD8 ratio <1, and had increased IgG titers to CMV (p < 0.01), but not to EBV, compared to subjects with CD4:CD8 ratio >1. The older adults with inverted CD4:CD8 ratio had impairments in some cognitive dimensions and had more functional disability and dependency (p = 0.01) than subjects with CD4:CD8 ratio >1. The lymphocyte subsets did not vary between groups. The increased CMV-IgG titers alone contributed to 8× higher chance to invert CD4:CD8 T cell ratio (OR 8.12, 95% CI 1.74-37.88, p < 0.01).

Our data further indicate the role of CMV on circulating T cells, poor cognition and functional disability/dependency during aging.