T-cell Tolerance Following Bacterial Glutamic Acid Decarboxylase (GAD) Feeding in Streptozotocin-induced Diabetes

Abstract

<span><b>Background</b>: </span> <span>Autoimmune type 1 diabetes mellitus is caused by T-cell mediated</span> <span>immune destruction of the insulin-producing <span lang="JA">β</span>-cell in pancreatic islets of Langerhans.</span> <span>Specificity of the auto-antibodies and of the auto-reactive T-cells has been investigated,</span> <span>in which several auto-antigens were proposed. </span><span><br/><b>Objective</b>: </span><span>To determine</span> whether glutamic acid decarboxylase (GAD) feeding would induce oral tolerance of either T-cell or B-cell compartment in streptozotocin (STZ) diabetic rats. <span><span><br/><b>Methods</b>:</span></span> Rats in the experimental group were fed 2 mg/kg of GAD (extracted from <span><em><span>Escherichia</span></em></span> coli <em><span><span>) 14 days before intra-peritoneal injections of streptozotocin (30 mg/kg</span></span></em> body weight for 5 consecutive days). Two control groups were considered: diabetic control group, which underwent STZ injections without receiving GAD, and normal control group. Systemic response was compared between the three groups. T-cells response was assessed by a proliferation assay of spleen cells and those of the B-cells by enzyme-linked immunosorbent assay (ELISA) for anti-GAD specific antibodies in serum. <span><span><br/><b>Results</b>: </span><span>Compared with the diabetic control group, a significant reduction</span></span> was observed only in the proliferative response of spleen cells, but not in the level of anti-GAD antibody. <span><span><br/><b>Conclusion</b>: </span><span>GAD feeding induces systemic T-cell tolerance in</span></span> STZ-induced diabetes.