A longitudinal study of the stability, variability, and interdependencies among late-differentiated T and NK cell subsets in older adults

The stability and variability of older adults’ late-differentiated peripheral blood T and natural killer (NK) cells over time remains incompletely quantified or understood. We examined the variability and change over time in T and NK cell subsets in a longitudinal sample of older adults; the effects of sex, cytomegalovirus (CMV) serostatus, and chronic disease severity on immune levels and trajectories; and interdependencies among T and NK cell subsets. Older adults (N = 149, age 64–94 years, 42% male) provided blood every 6 months for 2.5 years (up to 5 waves) to evaluate late-differentiated CD8 T cells (CD28− CD57+) and CD56 ^dim NK cells (CD57+, NKG2C+, FcɛRIγ−). In multilevel models, most of the variance in immune subsets reflected stable differences between people. However, CD56 ^dim NK cell subsets (CD57+ and FcɛRIγ−) also increased with age, whereas T cell subsets did not. Independent of age, all subsets examined were higher in CMV-positive older adults. Men had higher levels of CD56 ^dim CD57+ than women. Chronic disease was not associated with any immune subset investigated. T and NK cell subsets correlated within each cell type, but interdependencies differed by CMV serostatus. Our results suggest the accumulation of these stable cell populations may be driven less by chronological aging, even less by chronic disease severity, and more by CMV, which may differentially skew T and NK cell differentiation.