Involvement of Gut Immune System in the pathogenesis of type 1 diabetes: detection of T cell reactivity to Gliadin

摘要: Accumulating data indicate that a dysregulation of the gut immune system may play role in development Beta cell autoimmunity and type 1 diabetes (T1D). The aim this study was to determine possible link between T1D, particular, gliadin as T antigen human T1D. Peripheral blood mononuclear cells (PBMC) were isolated from 25 children with T1D (aged 3.4 19.6 yrs), 22 healthy controls (HC) 3.5 17 both negative for anti-endomysial anti-human tissue transglutaminase antibodies 15 celiac disease (CD) 2.2 13.3 yrs). In first part study, 6 5 CD HC, PBMC cultured or without OKT3 plus anti-CD28mAb. After 18 hours expression β7 integrin determined by flow cytometry. In patients we observed higher Beta7 on memory CD4+ cells. polyclonal stimulation found significant reduction compared controls. second 19 10 peptic-tryptic digest (PTG) and/or transgluatminase-treated (TG)-PTG at increasing concentrations, left un-stimulated. proliferation assessed day [3H]-thymidine incorporation assay. We also IFN-gamma IL-4 production culture supernatants ELISA studied cytometry. In detected dose-response PTG TG-PTG maximal concentration 100 µg/ml. 7 out 11 (64%) responded µg /ml PTG. Mean index (SI) than HC (2,95±2 vs.1,3±0,6 respectively, p=0,02). When stimulated 13 (54%) 2 3 (67%) showed proliferative response (T1D 2,4±2 vs. 1,5±0,7). In responders (43%) but not induced production. patient identified, after TG-PTG, discrete population β7hi+ cells. Our show expressing high levels are detectable peripheral an enhanced cell-mediated gluten-specific immunity patients. This supports hypothesis oral proteins is altered patients. Long term follow-up necessary establish whether these subjects increased risk developing disease.