Inhibition of reovirus-stimulated murine natural killer cell cytotoxicity by cyclosporine.
Reovirus type 3 is a double-stranded RNA virus that is a potent inducer of murine natural killer (NK) cell cytotoxicity, most likely as a result of virus-induced interferon production. We determined that reovirus was an effective inducer of high levels of NK cytotoxicity. A single injection of cyclosporine (CS), administered concurrently with reovirus or delayed until three days after injecting CS, significantly inhibited NK cytotoxicity. CS significantly suppressed reovirus-induced NK cytotoxicity when added directly to the chromium-release assay. We determined that CS inhibited the ability of murine spleen cells to form conjugates with YAC-1 tumor target cells. Finally, CS was shown to directly inhibit reovirus replication in vitro. Our results demonstrate that CS is an effective inhibitor of reovirus-induced NK cytotoxicity and suggest that inhibition occurs through multiple mechanisms including direct effects on the NK cells and direct inhibition of virus replication.
Department of Health Sciences, University of Wisconsin-Milwaukee 53201, USA.
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D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D012087:Reoviridae / Q000187:drug effects* / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects
D016572:Cyclosporine