Diabetogenic T Cells Induce Autoimmune Diabetes In BALB/c Mice

ObjectiveTo investigate the role of T cell and its subsets in the induction of insulitis and type 1 diabetes mellitus (T1DM) in BALB/c mice.MethodsAutoimmune diabetes mellitus was developed by intraperitoneal injection of 40 mg/kg streptozotocin (STZ) daily for 5 consecutive days in BALB/c mice as sources of donor cells. Spleen cells from diabetic mice were then cultured for 7 days in the stimulation of interleukin-2 (IL-2) to harvest diabetogenic T cells, which were subsequently transferred into normal BALB/c mice recipients. MTT, ELISA, and HE staining were used to analyze the lymphocyte proliferation, cytokine (IL-2, interferon-γ, IL-4, and IL-10) levels, and pathological changes in pancreatic islets.ResultsAs few as 3 × 106 diabetogenic T cells successfully induced diabetes mellitus in recipients pretreated with STZ twice, whereas transfer of equal amount of normal splenocytes, T cell-depleted diabetogenic splenocytes, or diabetogenic CD4+ T cells alone in recipients receiving STZ twice pretreatment was proved not to induce diabetes mellitus either. A markedly increased lymphocyte proliferation, high levels of interferon-γ and IL-2 in the supernatants of diabetogenic T cells were observed. In addition, a markedly enhanced lymphocyte proliferation, a high level of interferon-γ secretion in serum, and numerous lymphocytes infiltration in pancreatic islets were detected in the diabetic mice induced by diabetogenic T cells transfer.ConclusionA novel T1DM murine model is established in STZ-pretreated BALB/c mice by adoptive transfer of diabetogenic T cells. CD4+ T cells with interferon-γ may promote the onset of diabetes mellitus.