β-Cell-targeted expression of interferon-γ (IFN-γ) leads to pancreatitis and immune sensitization to β-cells. This transgenic model is used to explore the possible role of locally produced IFN-γ in loss of tolerance to β-cell-specific antigens in insulin-dependent diabetes mellitus (IDDM). The aim of the present study was to test if postnatal treatment with antibodies against IFN-γ could inhibit morphological changes in the IFN-γ transgenic pancreas, even though the transgene is expressed during embryogenesis. Treatment with a monoclonal rat anti-mouse IFN-γ antibody for 6 weeks, starting from 5 to 7 days of age, completely inhibited IFN-γ-induced morphological changes in the pancreas, and only a modest inflammatory reaction emerged after prolonged treatment for 12 weeks. The lack of morphological changes may reflect the ability of nonterminally differentiated neonatal pancreatic cells to compensate for transgene-induced pathological alterations occurring in utero prior to the antibody treatment. We conclude that inflammation and altered pancreas morphology in the transgenic mice is the result of the biological actions of IFN-γ and not by disrupted islet development due to transgene overexpression in the pancreatic β-cells. Furthermore, our treatment schedule can serve as a model for future intervention studies in the transgenic mice, elaborating the role of IFN-γ in localized inflammatory reactions, IDDM in particular.
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