Rapid NK cell differentiation in a population with near-universal human cytomegalovirus infection is attenuated by NKG2C deletions

Abstract

Natural killer (NK) cells differentiate and mature during the human life course; human cytomegalovirus (HCMV) infection is a known driver of this process. We have explored human NK cell phenotypic and functional maturation in a rural African (Gambian) populationwith a high prevalence of HCMV. The effect of age on the frequency, absolute number, phenotype, and functional capacity of NK cells was monitored in 191 individuals aged from 1 to 49 years. Increasing frequencies of NK cells with age were associated with increased proportions of CD56dim cells expressing the differentiation marker CD57 and expansion of the NKG2C1 subset. Frequencies of NK cells responding to exogenous cytokines declined with age in line with a decreased proportion of CD572 cells. These changes coincided with a highly significant drop in anti-HCMV IgG titers by the age of 10 years, suggesting thatHCMVinfection is brought under control asNKcells differentiate (or vice versa). Deletion at theNKG2Clocus was associated with a gene dose-dependent reduction in proportions of CD941 and CD571NKcells. Importantly, anti-HCMV IgG titers were significantly elevated inNKG2C2/2 children, suggesting that lack of expression ofNKG2Cmaybe associated with altered control of HCMV in childhood. (Blood. 2014;124(14):2213-2222).