Decreased in vitro type 1 immune response against coxsackie virus B4 in children with type 1 diabetes.
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 gamma-interferon (IFN-gamma). In children with type 1 diabetes, a decreased percentage of T-cells expressed CCR2, CXCR6, interleukin (IL)-18R, and IL-12Rbeta2-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-gamma 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 beta-cell damage.
Division of Pediatrics and Diabetes Research Centre, Department of Molecular and Clinical Medicine, Linköping University, S-581 85 Linköping, Sweden. susanne.skarsvik@imk.liu.se
Susanne
S
Skarsvik
Julia
J
Puranen
Jarno
J
Honkanen
Merja
M
Roivainen
Jorma
J
Ilonen
Hanna
H
Holmberg
Johnny
J
Ludvigsson
Outi
O
Vaarala
D001323:Autoantibodies / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D029822:Enterovirus B, Human / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008214:Lymphocytes / Q000276:immunology; D019707:Receptors, Chemokine / Q000276:immunology; D018121:Receptors, Cytokine / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine