In vivo kinetics of human natural killer cells:: the effects of ageing and acute and chronic viral infection

Human natural killer (NK) cells form a circulating population in a state of dynamic homeostasis. We investigated NK cell homeostasis by labelling dividing cells in vivo using deuterium-enriched glucose in young and elderly healthy subjects and patients with viral infection. Following a 24-hr intravenous infusion of 6,6-D-2-glucose, CD3(-) CD16(+) NK cells sorted from peripheral blood mononuclear cells (PBMC) by fluorescence-activated cell sorter (FACS) were analysed for DNA deuterium content by gas chromatography mass spectrometry to yield minimum estimates for proliferation rate (p). In healthy young adults (n = 5), deuterium enrichment was maximal similar to 10 days after labelling, consistent with postmitotic maturation preceding circulation. The mean (+/- standard deviation) proliferation rate was 4.3 +/- 2.4%/day (equivalent to a doubling time of 16 days) and the total production rate was 15 +/- 7.6 x 10(6) cells/l/day. Labelled cells disappeared from the circulation at a similar rate [6.9 +/- 4.0%/day; half-life (T-1/2) < 10 days]. Healthy elderly subjects (n = 8) had lower proliferation and production rates (P = 2.5 +/- 1.0%/day and 7.3 +/- 3.7 x 10(6) cells/l/day, respectively; P = 0.04). Similar rates were seen in patients chronically infected with human T-cell lymphotropic virus type I (HTLV-I) (P = 3.2 +/- 1.9%/day). In acute infectious mononucleosis (n = 5), NK cell numbers were increased but kinetics were unaffected (P = 2.8 +/- 1.0%/day) a mean of 12 days after symptom onset. Human NK cells have a turnover time in blood of about 2 weeks. Proliferation rates appear to fall with ageing, remain unperturbed by chronic HTLV-I infection and normalize rapidly following acute Epstein-Barr virus infection.