Coxsackievirus immunization delays onset of diabetes in non-obese diabetic mice.
Enteroviruses may be involved in the pathogenesis of Type 1 diabetes through different mechanisms including triggering of autoimmunity. The effect of immunization with coxsackievirus B4-E2 on diabetes incidence was studied in the non-obese diabetic mice, an animal model for human autoimmune insulin-dependent diabetes mellitus. The immunization delayed the onset of diabetes in the mice, and the effect was mediated at least partially by virus immunization-activated splenocytes as demonstrated by adoptive transfer experiments. Immunization resulted in a strong humoral immune response against the immunizing virus, formalin-inactivated coxsackievirus B4-E2. Cell-mediated immune response to virus antigen was characterised by interferon gamma and interleukin 10 secretion. The immunization also resulted in increased antibody levels against several beta-cell autoantigens. By using epitope mapping we were able to show that in addition to reactivity with the known epitopes of viral proteins and tyrosine phosphatase IA-2 or heat shock protein 60, responses to some other regions of autoantigens were enhanced. In preproinsulin, the response was restricted against an antigenic region earlier identified as DR4-dependent epitope. This reactivity can not be explained by homologous amino acid sequences and it is possible that enterovirus immunization might change the autoantigen specific TH1/TH2 balance in non-obese diabetic mice. In conclusion, our results suggest that coxsackievirus immunization increased humoral immune response to beta cell autoantigens and this was associated with a less destructive pathology for spontaneous diabetes in non-obese diabetic mice.
Davydova
B
B
Enterovirus Laboratory, National Public Health Institute (KTL), Helsinki, Finland.
Härkönen
T
T
Kaialainen
S
S
Hovi
T
T
Vaarala
O
O
Roivainen
M
M
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D003384:Coxsackievirus Infections / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000276:immunology*; D018604:Epitope Mapping; D005260:Female; D006801:Humans; D007114:Immunization; D015994:Incidence; D007515:Islets of Langerhans / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data
D000914:Antibodies, Viral; D000956:Antigens, Viral; D001324:Autoantigens