NK cell response to viral infections in beta 2-microglobulin-deficient mice.
Because class I MHC Ags have been implicated as modulators of target cell sensitivity to NK cell-mediated lysis, the regulation of virus infections and the fate of NK cells and their natural targets was examined 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 choriomeningitis 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-GM1 markedly enhanced the synthesis of MCMV but had no effect on the synthesis of LCMV in either strain of mouse. Analysis of naturally NK cell-sensitive thymocyte targets from these virus-infected -/- mice revealed no cell surface expression of class I MHC detectable by conformation-dependent or -independent Abs, but the virus infections enhanced class I expression on thymocytes from +/+ mice. The sensitivity of +/+ thymocytes to NK cell-mediated lysis was markedly reduced after in vivo poly inosinic:cytidylic and treatment or viral infection; in contrast, the sensitivity of the -/- thymocytes was significantly less affected by poly inosinic:cytidylic 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-sensitive virus (MCMV) nor do they protect a NK-resistant virus (LCMV) from the antiviral activity of NK cells.
Tay
C H
CH
Department of Pathology, University of Massachusetts Medical Center, Worcester 01655.
Welsh
R M
RM
Brutkiewicz
R R
RR
D000818:Animals; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000096:biosynthesis / Q000276:immunology*; D006566:Herpesviridae Infections / Q000276:immunology*; D007372:Interferons / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000276:immunology*; D011070:Poly I-C / Q000494:pharmacology; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000276:immunology
D006183:H-2 Antigens; D001613:beta 2-Microglobulin; D007372:Interferons; D011070:Poly I-C