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. 2007 Jun;121(2):258-65.
doi: 10.1111/j.1365-2567.2007.02573.x. Epub 2007 Mar 7.

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

Yan Zhang  1 , Diana L Wallace, Catherine M de Lara, Hala Ghattas, Becca Asquith, Andrew Worth, George E Griffin, Graham P Taylor, David F Tough, Peter C L Beverley, Derek C Macallan
Affiliations

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

Yan Zhang et al. Immunology. 2007 Jun.

Abstract

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 approximately 10 days after labelling, consistent with postmitotic maturation preceding circulation. The mean (+/- standard deviation) proliferation rate was 4 x 3 +/- 2 x 4%/day (equivalent to a doubling time of 16 days) and the total production rate was 15 +/- (7 x 6) x 10(6) cells/l/day. Labelled cells disappeared from the circulation at a similar rate [6 x 9 +/- 4 x 0%/day; half-life (T((1/2))) < 10 days]. Healthy elderly subjects (n=8) had lower proliferation and production rates (P=2 x 5 +/- 1 x 0%/day and 7 x 3 +/- (3 x 7) x 10(6) cells/l/day, respectively; P=0 x 04). Similar rates were seen in patients chronically infected with human T-cell lymphotropic virus type I (HTLV-I) (P=3 x 2 +/- 1 x 9%/day). In acute infectious mononucleosis (n=5), NK cell numbers were increased but kinetics were unaffected (P=2 x 8 +/- 1 x 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.

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Figures

Figure 1
Figure 1
Labelling of natural killer (NK) cells following infusion of 6,6-2H2-glucose in (a) healthy young subjects, (b) healthy elderly subjects and (c) young subjects with acute Epstein–Barr virus (EBV) infection. Values represent the mean ± standard deviation for labelled cells at time-points after commencement of infusion for 24 hr. Subjects infected with human T-cell lymphotropic virus type I (HTLV-I) are not shown as blood samples were not taken after day 10.
Figure 2
Figure 2
Time–course of natural killer (NK) cell numbers in acute infectious mononucleosis. Time is from the beginning of in vivo labelling. Curves represent individual subjects: M01 (filled square), M03 (filled diamond), M04 (triangle), M05 (open square) and M06 (open diamond).
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