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

Document Type: Original Article

Authors

1 Department of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Immunology and

3 Autoimmune Disease Research Centre, Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

4 Institute of Biochemistry and Biophysics, Tehran University, Tehran, Iran, and

5 Department of Pathology, Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Background: Autoimmune type 1 diabetes mellitus is caused by T-cell mediated immune destruction of the insulin-producing β-cell in pancreatic islets of Langerhans. Specificity of the auto-antibodies and of the auto-reactive T-cells has been investigated, in which several auto-antigens were proposed.
Objective:
To determine whether glutamic acid decarboxylase (GAD) feeding would induce oral tolerance of   either T-cell or B-cell compartment in streptozotocin (STZ) diabetic rats.
Methods:
Rats in the experimental group were fed 2 mg/kg of GAD (extracted from Escherichia coli ) 14 days before intra-peritoneal injections of streptozotocin (30 mg/kg 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.
Results:
Compared with the diabetic control group, a significant reduction
was observed only in the proliferative response of spleen cells, but not in the level of anti-GAD antibody.
Conclusion:
GAD feeding induces systemic T-cell tolerance in
STZ-induced diabetes.

Keywords