Decreased In Vitro Type 1 Immune Response Against Coxsackie Virus B4 in Children With Type 1 Diabetes
- Susanne Skarsvik1,
- Julia Puranen1,
- Jarno Honkanen2,
- Merja Roivainen3,
- Jorma Ilonen4,
- Hanna Holmberg1,
- Johnny Ludvigsson1 and
- Outi Vaarala12
- 1Division of Pediatrics and Diabetes Research Centre, Department of Molecular and Clinical Medicine, Linköping University, Linköping, Sweden
- 2Laboratory for Immunobiology, Department of Viral Diseases and Immunology, National Public Health Institute, Helsinki, Finland
- 3Enterovirus Laboratory, Department of Viral Diseases and Immunology, National Public Health Institute, Helsinki, Finland
- 4Turku Immunology Centre and Department of Virology, University of Turku, Turku, Finland
- Address correspondence and reprint requests to Dr. Susanne Skarsvik, Clinical and Experimental Research, Faculty of Health Sciences, Linköping University, S-581 85 Linköping, Sweden. E-mail: susanne.skarsvik{at}imk.liu.se
Abstract
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.
Footnotes
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CVB4, Coxsackie virus B4; IFN-γ, γ-interferon; IL, interleukin; PBMC, peripheral blood mononuclear cell.
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- Accepted January 3, 2006.
- Received May 18, 2005.
- DIABETES
