Coxsackievirus immunization delays onset of diabetes in non-obese diabetic mice
2003 (English)In: Journal of Medical Virology, ISSN 0146-6615, Vol. 69, no 4, 510-520 p.Article in journal (Refereed) Published
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 responseto 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 A-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. © 2003 Wiley-Liss, Inc.
Place, publisher, year, edition, pages
2003. Vol. 69, no 4, 510-520 p.
Antibodies, Beta-cell autoantigen, Coxsackievirus, Enterovirus, Immunization, Insulin-dependent diabetes mellitus, Non-obese diabetic mice, T-cell responses
National CategoryMedical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-46679DOI: 10.1002/jmv.10339OAI: oai:DiVA.org:liu-46679DiVA: diva2:267575