Immune tolerance induced by adoptive transfer of dendritic cells in an insulin-dependent diabetes mellitus murine model
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-macrophage
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 modulate
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 observed
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 associated
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.
Keywords:
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-macrophage
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 modulate
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 observed
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 associated
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.