ROLE OF NK CELLS IN IMMUNOMODULATOR-MEDIATED RESISTANCE TO HERPESVIRUS-INFECTION

Seven chemically diverse biological response modifiers (BRM) were comp ared for antiviral activity in intact and NK cell-depleted CD-1 mice. Both spontaneous and BRM-induced splenic NK cell cytotoxicity were dep leted for at least 5 days following treatment with the monoclonal anti body NK1.1. Antiviral protection of standard doses of MVE-2, pIC, pICL C, rmIFN-tau and CL246,738 against lethal MCMV or HSV-2 infections was not abrogated by NK cell depletion, demonstrating that NK cells are n ot required for BRM-induced antiviral activity against these herpesvir uses. When mice were treated with 100000 U of rHuIFN-alpha B/D, NK cel ls 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 low er doses, the activity of rHuIFN-alpha B/D against MCMV appeared depen dent upon the presence of NK cells. A similar dose-related requirement for NK cells was observed for activity of OK-432. Thus, at higher dos es of rHuIFN-alpha B/D and OK-432, elements of the natural immune syst em in addition to or other than NK cells are apparently involved, whil e at lower doses NK cells appear to play a more important role in anti viral protection against MCMV infection.