Role of NK cells in immunomodulator-mediated resistance to herpesvirus infection.
Seven chemically diverse biological response modifiers (BRM) were compared for antiviral activity in intact and NK cell-depleted CD-1 mice. Both spontaneous and BRM-induced splenic NK cell cytotoxicity were depleted for at least 5 days following treatment with the monoclonal antibody NK1.1. Antiviral protection of standard doses of MVE-2, pIC, pICLC, rmIFN-tau and CL246,738 against lethal MCMV or HSV-2 infections was not abrogated by NK cell depletion, demonstrating that NK cells are not required for BRM-induced antiviral activity against these herpesviruses. When mice were treated with 100,000 U of rHuIFN-alpha B/D, NK cells were not required for activity against MCMV, while at a dose of 25,000 U, NK cells appeared to be partially required against MCMV. At lower doses, the activity of rHuIFN-alpha B/D against MCMV appeared dependent upon the presence of NK cells. A similar dose-related requirement for NK cells was observed for activity of OK-432. Thus, at higher doses of rHuIFN-alpha B/D and OK-432, elements of the natural immune system in addition to or other than NK cells are apparently involved, while at lower doses NK cells appear to play a more important role in antiviral protection against MCMV infection.
Medical College of Pennsylvania, Department of Microbiology and Immunology, Philadelphia 19129.
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Kunder
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Wu
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Morahan
D000276:Adjuvants, Immunologic / Q000378:metabolism*; D000818:Animals; D003586:Cytomegalovirus Infections / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D006561:Herpes Simplex / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology*; D007113:Immunity, Innate / Q000187:drug effects; D016898:Interferon-alpha / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D008212:Lymphocyte Depletion; D051379:Mice; D008815:Mice, Inbred Strains; D010844:Picibanil / Q000494:pharmacology; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology
D000276:Adjuvants, Immunologic; D016898:Interferon-alpha; D010844:Picibanil