title: In vivo kinetics of human natural killer cells: the effects of ageing and acute and chronic viral infection.
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.
authors.affiliation: Centre for Infection, Division of Cellular & Molecular Medicine, St George's, University of London, London, UK.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Diana L
authors.initials: DL
authors.lastname: Wallace
authors.forename: Catherine M
authors.initials: CM
authors.lastname: de Lara
authors.forename: Hala
authors.initials: H
authors.lastname: Ghattas
authors.forename: Becca
authors.initials: B
authors.lastname: Asquith
authors.forename: Andrew
authors.initials: A
authors.lastname: Worth
authors.forename: George E
authors.initials: GE
authors.lastname: Griffin
authors.forename: Graham P
authors.initials: GP
authors.lastname: Taylor
authors.forename: David F
authors.initials: DF
authors.lastname: Tough
authors.forename: Peter C L
authors.initials: PC
authors.lastname: Beverley
authors.forename: Derek C
authors.initials: DC
authors.lastname: Macallan
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D049109:Cell Proliferation; D002908:Chronic Disease; D005260:Female; D015490:HTLV-I Infections / Q000276:immunology; D006801:Humans; D007244:Infectious Mononucleosis / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D014777:Virus Diseases / Q000276:immunology*