Decreased in vitro type 1 immune response against coxsackie virus B4 in children with type 1 diabetes
2006 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 55, no 4, 996-1003 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
American Diabetes Association , 2006. Vol. 55, no 4, 996-1003 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-34899DOI: 10.2337/diabetes.55.04.06.db05-0630PubMedID: 16567521Local ID: 23891OAI: oai:DiVA.org:liu-34899DiVA: diva2:255747