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Coxsackievirus immunization delays onset of diabetes in non-obese diabetic mice
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- Davydova, B. (author)
- Enterovirus Laboratory, Natl. Public Health Institute (KTL), Mannerheimintie 166, FIN-00300 Helsinki, Finland
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- Harkonen, T. (author)
- Härkönen, T., Enterovirus Laboratory, Natl. Public Health Institute (KTL), Mannerheimintie 166, FIN-00300 Helsinki, Finland
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- Kaialainen, S. (author)
- Enterovirus Laboratory, Natl. Public Health Institute (KTL), Mannerheimintie 166, FIN-00300 Helsinki, Finland
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- Enterovirus Laboratory, Natl Public Health Institute (KTL), Mannerheimintie 166, FIN-00300 Helsinki, Finland Härkönen, T., Enterovirus Laboratory, Natl. Public Health Institute (KTL), Mannerheimintie 166, FIN-00300 Helsinki, Finland (creator_code:org_t)
- 2003-02-24
- 2003
- English.
- In: Journal of Medical Virology. - : Wiley. - 0146-6615 .- 1096-9071. ; 69:4, s. 510-520
- Journal article (peer-reviewed)
Abstract
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- 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.
Keyword
- Antibodies
- Beta-cell autoantigen
- Coxsackievirus
- Enterovirus
- Immunization
- Insulin-dependent diabetes mellitus
- Non-obese diabetic mice
- T-cell responses
- MEDICINE
- MEDICIN
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- ref (subject category)
- art (subject category)
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