Immune tolerance induced by adoptive transfer of dendritic cells in an insulin‐dependent diabetes mellitus murine model 1

Abstract Aim: 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.