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Immune tolerance induced by adoptive transfer of dendritic cells in an insulin-dependent diabetes mellitus murine model

AbstractAim:To investigate the effect and underlying mechanisms of immune-tolerance induced by the adoptive transfer of bone marrow (BM)-derived dendritic cells (DC) in insulin-dependent diabetes mellitus (IDDM) mice.Methods:The IDDM model was established by a low dose of streptozotocin (STZ) in Balb/c mice. Two DC subpopulations were generated from the BM cells with granulocyte-macroph-age colony-stimulating factor with or without interleukin-4. The purity and the T cell stimulatory capability of DC were identified. These cells were used to modu late autoimmune response in pre-diabetic mice. Blood glucose was examined weekly; pancreas tissues were taken for histopathological analysis, and CD4+ T cells were isolated to detect lymphocyte proliferation by MTT assay and the ratio of CD4+CD25+ T cells by fluorescence-activated cell sorting (FACS). The cytokine secretion was determined by ELISA analysis.Results:Two DC subsets were generated from BM, which have phenotypes of mature DC (mDC) and immature DC (iDC), respectively. The level of blood glucose decreased significantly by transferring iDC (P<0.01) rather than mDC. Less lymphocyte infiltration was ob served in the islets, and pancreatic structure was intact. In vitro, proliferation of lymphocytes decreased and the proportion of CD4+CD25+ T cells increased remarkably, compared with the mDC-treated groups (P<0.05), which were associ ated with increased level of the Th2 cytokine and reduced level of the Th1 cytokine after iDC transfer.Conclusion:Our data showed that iDC transfer was able to confer protection to mice from STZ-induced IDDM. The immune-tolerance to IDDM may be associated with promoting the production of CD4+CD25+ T cells and inducing regulatory Th2 responses in vivo.