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C57BL/KsJ mice carrying homozygous db/db mutation (db/db mice) are characterized by extreme obesity and early onset of hyperglycemia. In an attempt to rectify diabetes of these mice, a pancreatic beta cell line MIN6, which retains glucose-inducible insulin secretion, was transplanted subcutaneously into the back of the mice. Glucose and insulin levels of individual mice were examined biweekly and their weight gain weekly. All mice were sacrificed at 100 days after the transplantation of MIN6 cells. In db/db mice that had received MIN6 cells, blood insulin levels were restored and blood glucose levels were reduced to those of non-diabetic mice, although they remained obese. Glucose tolerance test suggested that transplanted MIN6 cells responded to loaded glucose as beta cells of non-diabetic mice. Immunohistochemical study showed that transplanted MIN6 cells produced insulin. Fatty liver associated with diabetes mellitus observed in db/db mice was not found in the MIN6 cell-transplanted mice. Implication of the results is discussed with reference to potential therapies for severe diabetes.

We report in this paper on obvious fibrotic lesions in the liver of mice undergoing specified graft-versus-host reaction (GVHR). B6 CD8+ splenocytes were transferred into (bm 12 × bm 1)F1 mice to induce GVHR. Recipient mice had been thymectomized and administrated with anti-CD8 monoclonal antibody (mAb) to deplete CD8+ cells from the hosts. Two weeks after the mAb administration, recipient mice were injected with B6 CD8+ cells and sacrificed further two or four weeks later for analyzing hepatic lesions histopathologically. Light microscopic analyses revealed the presence of concentric fibrosis around both small and large duct levels and the infiltration of mononuclear cells into portal areas. Focal necrrosis of hepatocytes was also detected electron-microscopically. These findings suggest that CD8+ T lymphocytes might play an important role in the induction of fibrotic lesions in the liver.

In this paper, we examined the induction of autoimmune-like histologic changes in the liver and other organs of mice undergoing graft-versus-host reaction (GVHR) with MHC class I disparity by the administration of bacterial lipopolysaccharide (LPS), on the assumption that stimulation with LPS could be an exacerbating factor. Spleen cells of C57BL 6 (B6) mice were injected twice into (B6 × bml) F1 recipient mice at an interval of 7 days to induce MHC class I GVHR and then challenged with 1 μg of LPS intravenously on the next day of the cell transfer. The hepatic lesions of the group of MHC class I GVHR mice challenged with LPS showed marked cellular infiltration at the portal area and focal necrosis was observed in the hepatic lobule. The major infiltrating cells were CD8 + , and others including CD4 + cells being of minor populations. In addition, ductal lesions in extrahepatic organs, including the pancreas and salivary glands also showed marked cellular infiltration. Thus, we have demonstrated that LPS induced ductal lesions in mice with MHC class I disparity. CD8 + cells were detected at the destructive hepatic lesions, which might be effector cells. These findings indicate that LPS might be one of the potential factors which augment autoimmune-like lesions.