NK CELL RESPONSE TO VIRAL-INFECTIONS IN BETA-2-MICROGLOBULIN-DEFICIENT MICE

Because class 1 MHC Ags have been implicated as modulators of target c ell sensitivity to NK cell-mediated lysis, the regulation of virus inf ections and the fate of NK cells and their natural targets was examine d in beta(2)-microglobulin-deficient mice, which have defective class I MHC expression. Infections with either the NK cell-sensitive murine cytomegalovirus (MCMV) or the NK cell-resistant lymphocytic choriomeni ngitis virus (LCMV) significantly augmented NK cell activity in either C57BL/6 (+/+) or beta(2)-microglobulin knockout (-/-) mice. Depletion of NK cells in vivo with antiserum to asialo-GM, markedly enhanced th e synthesis of MCMV but had no effect on the synthesis of LCMV in eith er strain of mouse. Analysis of naturally NK cell-sensitive thymocyte targets from these virus-infected -/- mice revealed no cell surface ex pression of class 1 MHC detectable by conformation-dependent or -indep endent Abs, but the virus infections enhanced class I expression on th ymocytes from +/+ mice. The sensitivity of +/+ thymocytes to NK cell-m ediated lysis was markedly reduced after in vivo poly inosinic:cytidyl ic and treatment or viral infection; in contrast, the sensitivity of t he -/- thymocytes was significantly less affected by poly inosinic:cyt idylic acid treatment or viral infection. These data indicate that the normal expression of class I MHC Ags on NK cells or their targets is not required for the antiviral functions of NK cells against a NK-sens itive virus (MCMV) nor do they protect a NK-resistant virus (LCMV) fro m the antiviral activity of NK cells.