期刊
IMMUNOLOGY
卷 124, 期 2, 页码 215-222出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1365-2567.2007.02757.x
关键词
animal model; calcein; cytotoxicity; immunophenotyping; natural killer cell
类别
资金
- NCRR NIH HHS [RR000168, RR016001, P51 RR000168, R24 RR016001, K26 RR000168] Funding Source: Medline
- NIAID NIH HHS [P30 AI060354, AI067854, AI040101, U01 AI067854, R01 AI040101, AI060354, U19 AI067854] Funding Source: Medline
Non-human primates serve as key animal models for a variety of viral infections. To evaluate the contribution of natural killer (NK) cells to the immune-mediated control of these viruses in macaque monkeys, we have described a method for depleting NK cells in vivo by administration of anti-human CD16 mouse monoclonal antibody. Using a fluorometric NK-cell cytotoxicity assay, we show that most NK-cell cytotoxicity in rhesus monkey peripheral blood mononuclear cells resides in the CD16(+) and/or CD159A(+) subset of lymphocytes. The anti-human CD16 antibody, 3G8, binds to subsets of rhesus monkey lymphocytes and monocytes but not to neutrophils. Intravenous administration of 10-50 mg/kg of 3G8 to normal rhesus monkeys resulted in anti-CD16 antibody persistence in the plasma for 1-3 weeks. This treatment also depleted 80-90% of CD3(-) CD159A(+) lymphocytes, putative NK cells, from blood for at least 1 week and was associated with the loss of NK-cell cytotoxicity when evaluated by in vitro assays. Using this method, transient depletion of NK cells from two rhesus monkeys chronically infected with simian immunodeficiency virus failed to cause changes in virus replication. These studies describe a non-human primate model for in vivo NK-cell depletion and suggest a limited role for cytotoxic CD16(+) NK cells in controlling AIDS virus replication during chronic infection.
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