NK cell response to viral infections in beta 2-microglobulin-deficient mice
Immunology & Virology Program
Department of Pathology
Medical Subject Headings
Animals; Cytotoxicity Tests, Immunologic; Flow Cytometry; H-2 Antigens; Herpesviridae Infections; Interferons; Killer Cells, Natural; Lymphocytic Choriomeningitis; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Knockout; Muromegalovirus; Poly I-C; beta 2-Microglobulin
Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences
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.
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Citation: J Immunol. 1995 Jan 15;154(2):780-9.