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- Title
In vivo kinetics of human natural killer cells: the effects of ageing and acute and chronic viral infection.
- Authors
Zhang, Yan; Wallace, Diana L.; de Lara, Catherine M.; Ghattas, Hala; Asquith, Becca; Worth, Andrew; Griffin, George E.; Taylor, Graham P.; Tough, David F.; Beverley, Peter C. L.; Macallan, Derek C.
- 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-D2-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 ∼ 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 × 106 cells/l/day. Labelled cells disappeared from the circulation at a similar rate [6·9 ± 4·0%/day; half-life ( T½) < 10 days]. Healthy elderly subjects ( n = 8) had lower proliferation and production rates ( P = 2·5 ± 1·0%/day and 7·3 ± 3·7 × 106 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.
- Subjects
KILLER cells; HOMEOSTASIS; CELL division; GLUCOSE; VIRUS diseases
- Publication
Immunology, 2007, Vol 121, Issue 2, p258
- ISSN
0019-2805
- Publication type
Article
- DOI
10.1111/j.1365-2567.2007.02573.x