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 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.
Zhang
Yan
Y
Centre for Infection, Division of Cellular & Molecular Medicine, St George's, University of London, London, UK.
Wallace
Diana L
DL
de Lara
Catherine M
CM
Ghattas
Hala
H
Asquith
Becca
B
Worth
Andrew
A
Griffin
George E
GE
Taylor
Graham P
GP
Tough
David F
DF
Beverley
Peter C L
PC
Macallan
Derek C
DC
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*