Coxsackievirus B4 infection of the mouse pancreas: the role of natural killer cells in the control of virus replication and resistance to infection.
The role of natural killer (NK) cells in the early immune response to a pancreatropic isolate of coxsackievirus B4 (CVB4) was investigated in a murine model of pancreatitis. Endogenous (background) NK cell activity in fresh spleen effector cells from eight mouse strains was compared with virus-augmented NK cell activity 4 days post-infection (p.i.). A significant virus-induced increase (P less than or equal to 0.003) in NK cell activity was seen in seven of eight infected mouse strains, when virus titres in the pancreas were beginning to fall. Lesions in the exocrine pancreas were least extensive in the three strains with the highest endogenous NK cell activity. In C3H/HeJ mice that had been depleted of NK cells prior to infection with a low virus concentration, resistance to infection of the pancreas was completely abolished; myocarditis was also observed in one of these animals. Thus, NK cells may limit virus replication in the pancreas and play a role in resistance in C3H/HeJ mice. Virus-specific neutralizing antibody was not detected in the serum until 5 to 6 days p.i. in most strains and did not appear to influence pancreatic virus titres. It may be significant that CVB4 infection did not induce the expression of major histocompatibility complex (MHC) class I molecules on target acinar cells. With certain tumour cells, an inverse relationship between MHC class I expression and susceptibility to NK cell-mediated lysis is well documented.
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Department of Immunology, London Hospital Medical College, U.K.
Festenstein
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D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D004770:Enterovirus / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D007113:Immunity, Innate / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009500:Neutralization Tests; D010195:Pancreatitis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D014709:Vero Cells; D014779:Virus Replication
D000914:Antibodies, Viral; D015395:Histocompatibility Antigens Class I