PMID- 17346281 OWN - NLM STAT- MEDLINE DCOM- 20070618 LR - 20220224 IS - 0019-2805 (Print) IS - 1365-2567 (Electronic) IS - 0019-2805 (Linking) VI - 121 IP - 2 DP - 2007 Jun TI - In vivo kinetics of human natural killer cells: the effects of ageing and acute and chronic viral infection. PG - 258-65 AB - 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. FAU - Zhang, Yan AU - Zhang Y AD - Centre for Infection, Division of Cellular & Molecular Medicine, St George's, University of London, London, UK. FAU - Wallace, Diana L AU - Wallace DL FAU - de Lara, Catherine M AU - de Lara CM FAU - Ghattas, Hala AU - Ghattas H FAU - Asquith, Becca AU - Asquith B FAU - Worth, Andrew AU - Worth A FAU - Griffin, George E AU - Griffin GE FAU - Taylor, Graham P AU - Taylor GP FAU - Tough, David F AU - Tough DF FAU - Beverley, Peter C L AU - Beverley PC FAU - Macallan, Derek C AU - Macallan DC LA - eng GR - Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070307 PL - England TA - Immunology JT - Immunology JID - 0374672 SB - IM MH - Acute Disease MH - Adult MH - Aged MH - Aged, 80 and over MH - Aging/*immunology MH - Cell Proliferation MH - Chronic Disease MH - Female MH - HTLV-I Infections/immunology MH - Humans MH - Infectious Mononucleosis/immunology MH - Killer Cells, Natural/*immunology MH - Lymphocyte Count MH - Male MH - Middle Aged MH - Virus Diseases/*immunology PMC - PMC2265941 EDAT- 2007/03/10 09:00 MHDA- 2007/06/19 09:00 PMCR- 2008/06/01 CRDT- 2007/03/10 09:00 PHST- 2007/03/10 09:00 [pubmed] PHST- 2007/06/19 09:00 [medline] PHST- 2007/03/10 09:00 [entrez] PHST- 2008/06/01 00:00 [pmc-release] AID - IMM2573 [pii] AID - 10.1111/j.1365-2567.2007.02573.x [doi] PST - ppublish SO - Immunology. 2007 Jun;121(2):258-65. doi: 10.1111/j.1365-2567.2007.02573.x. Epub 2007 Mar 7.