Ricerc@Sapienza

Besides their innate ability to rapidly produce effector cytokines and kill virus-infected or transformed cells, natural killer (NK) cells display a strong capability to adapt to environmental modifications. In this context, cytomegalovirus (CMV) infection drives an epigenetically-shaped, long-living, hyperfunctional NK subpopulation dubbed adaptive or memory NK cells which are endowed with an enhanced ability to mediate CD16-dependent cytotoxicity and IFN-gamma production. In humans, memory NK cells are commonly defined by either a lack of the signaling adaptor chain FcepsilonRIgamma and/or a gain of the activating receptor NKG2C, along with increased levels of CD57 maturation marker. Although the frequencies of FcepsilonRIgamma- and NKG2C+ NK cells positively correlate, such phenotypic markers are often dissociated, thus evidencing a remarkable degree of heterogeneity within memory NK cell population.
In a large cohort of healthy CMV seropositive individuals we want to characterize memory NK cell subpopulations by evaluating their frequency and absolute number, the molecular and metabolic signature relevant for their survival and/or self-renewal advantage, as well as the capability to mediated antibody (Ab)-dependent effector functions and to proliferate in response to CD16 stimulation.