The pathogenicity of polyclonal rabbit anti-mouse platelet antibody was strongly exacerbated in mice acutely infected with LDV.7,8 This led to severe thrombocytopenia and to the development of purpuric lesions reminiscent of human thrombocytopenic purpura.7 A similar enhancement of antibody pathogenicity was observed in LDV-infected mice that received monoclonal anti-mouse platelet autoantibodies, derived either from (NZB x BXSB)F1 mice or from animals that developed an autoimmune anti-platelet response after immunization with rat platelets.9 Infection with mouse hepatitis virus (MHV) resulted in the same enhancing effect of autoantibody pathogenicity.7 Moreover, anemia induced by an anti-erythrocyte monoclonal antibody was also strongly exacerbated in mice infected with LDV.10 Interestingly, this consequence of LDV infection was found with an IgG2a autoantibody that induces anemia through phagocytosis, but not with an IgG1 autoantibody that lead to a similar disease through distinct mechanisms.11 Because enhancement of anti-platelet antibody pathogenicity by LDV infection required the presence of the Fc fraction of this antibody,7 these results suggested that phagocytosis of autoantibody-opsonized target cells was increased in infected mice. Indeed, ex vivo phagocytosis of autoantibody-coated erythrocytes was more efficient with macrophages derived from LDV acutely infected mice than from uninfected animals.10 Moreover, LDV-enhanced, antibody-mediated thrombocytopenia was inhibited by treatment with total immunoglobulins that block Fc-receptor-mediated phagocytosis of opsonized cells.7,8,12 Finally, LDV-infected mice were treated with clodronate-containing liposomes that destroy phagocytic macrophages in vivo13 and thus prevent autoimmune diseases that occur through this mechanism.14 This treatment prevented LDV-enhanced autoantibody-mediated autoimmune disease,7'8 as well as LDV-induced increase of ex vivo macrophage phagocytosis of opsonized red cells (Figure 1). Together, these results indicate that the pathogenic effect of LDV infection involves enhancement of the phagocytic activity of macrophages.
Because IFN-y is known to activate macrophages, the role of this cytokine in the enhancement of autoantibody-mediated disease by LDV was tested by using mice deficient for the IFN-y receptor,15 or neutralizing anti-IFN-y antibodies. The results of these experiments indicated that IFN-y secretion was required for the exacerbation of phagocytosis-mediated autoantibody autoimmune diseases by LDV infection.7,8
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