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.
al-Sheboul
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Department of Health Sciences, University of Wisconsin-Milwaukee 53201, USA.
Crosley
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Steele
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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