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Decreased in vitro type 1 immune response against coxsackie virus B4 in children with type 1 diabetes
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- Skarsvik, Susanne, 1978- (author)
- Linköpings universitet,Pediatrik,Hälsouniversitetet
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- Puranen, Julia (author)
- Linköpings universitet,Pediatrik,Hälsouniversitetet
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- Honkanen, Jarno (author)
- Laboratory for Immunobiology, Department of Viral Diseases and Immunology, National Public Health Institute, Helsinki, Finland
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- American Diabetes Association, 2006
- 2006
- English.
- In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 55:4, s. 996-1003
- Journal article (peer-reviewed)
Abstract
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- Enteroviruses, particularly Coxsackie virus B4 (CVB4), are considered to be involved in the pathogenesis of type 1 diabetes. We wanted to compare the characteristics of T-cell immune response to CVB4 in children with type 1 diabetes and healthy children with and without HLA risk-associated haplotypes (HLA-DR3-DQ2 or HLA-DR4-DQ8) for type 1 diabetes. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured with CVB4 and analyzed for cytokine and chemokine receptors by flow cytometry and for expression of transcription factors Tbet and GATA-3 by RT-PCR and Western blot. Culture supernatants were analyzed for secretion of γ-interferon (IFN-γ). In children with type 1 diabetes, a decreased percentage of T-cells expressed CCR2, CXCR6, interleukin (IL)-18R, and IL-12Rβ2-chain after in vitro stimulation with CVB4 in comparison with healthy children with or without HLA risk genotype. Moreover, we found that children with type 1 diabetes had decreased IFN-γ secretion and expression of Tbet, both on mRNA and protein level, in CVB4-stimulated PBMCs. Accordingly, children with type 1 diabetes show an impaired type 1 immune response against CVB4 compared with healthy children. This may lead to a delayed clearance of the virus and, at least partly, explain why children with type 1 diabetes may be more prone to CVB4 infections and related complications, such as β-cell damage.
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