Antibody-mediated immune enhancement in coxsackievirus B3 myocarditis.
The aim of the present study was to explore the contribution of antibody-mediated immune enhancement in coxsackievirus B3(CB3) infection. Murine macrophage-like P388D1 cells were exposed to various concentrations of anti-CB3 immunoglobulin G (anti-CB3 IgG) or the Fab fragment of anti-CB3 IgG, and were infected with CB3 in Experiment I. High concentrations of anti-CB3 IgG showed a virus-neutralizing activity; however, a subneutralizing antibody concentration of IgG significantly enhanced virus replication. This infectious enhancement was blocked not only by the pretreatment of heat-aggregated gamma-globulin but by a specific Fc receptor (Fc gamma III/II receptor) antibody treatment. In contrast, the Fab fragment of anti-CB3 IgG did not enhance CB3 infection, but showed a rational neutralizing activity to CB3. These findings suggest the presence of Fc receptor mediated enhancement of CB3 infection in vitro. In Experiment II, C(3)H/He mice were inoculated with various amounts of an amyocarditic variant of CB3 followed 15 days later by myocarditic CB3. By this rechallenge, myocarditis was not induced in the mice with high neutralizing antibody titers. There was an inverse relationship between preexisting neutralizing antibody titers and the severity of myocarditis. The severity of myocarditis and myocardial CB3 titers, however, were markedly enhanced in the mice with a subneutralizing level of immunity compared to those with no immunity. The distribution of myocardial Fc receptor-bearing cells and serum macrophage inflammatory protein-2 levels paralleled the severity of myocarditis. By another virus rechallenge in Experiment III, enhanced infection of CB3 was not observed in vivo. These findings suggest that antibody-mediated immune enhancement might be involved in the pathogenesis of CB3 myocarditis.
Kishimoto
Chiharu
C
Second Department of Internal Medicine and Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, 930-01, Japan. kkishi@kuhp.kyoto-u.ac.jp
Kurokawa
Masahiko
M
Ochiai
Hiroshi
H
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D002478:Cells, Cultured; D003384:Coxsackievirus Infections / Q000276:immunology*; D029822:Enterovirus B, Human; D019402:Macrophage Inflammatory Proteins / Q000276:immunology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology / Q000821:virology; D009336:Necrosis; D011961:Receptors, Fc / Q000502:physiology
D000914:Antibodies, Viral; D019402:Macrophage Inflammatory Proteins; D011961:Receptors, Fc