Rejection and histopathology of renal subcapsular fetal pig pancreas xenografts in normal and anti-CD4 monoclonal antibody-treated nonobese diabetic mice.
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Biomedical subjects
Publications and source records attributed to T E Mandel.
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The effect of oral administration of THI, a compound present in ammonia caramel food colouring, was studied in spontaneous and induced murine diabetes mellitus. Continuous administration of THI at 400 ppm in drinking water reduced the prevalence of spontaneous diabetes in female NOD/Lt mice from 63% in untreated controls to 8% in treated animals. Since cyclophosphamide (CP) accelerates and intensifies diabetes in NOD mice, we also studied the effect of THI in this model. Diabetes incidence was reduced from 100% in mice given only CP to 13-14% in mice given THI either concurrently or from 14 days previously. Histologically, THI greatly reduced the severity of insulitis. As measured by flow cytometry, all THI-treated mice had a 60-80% reduction in splenic CD4+ and CD8+ T cells. THI-treated mice showed no untoward effects and specifically no weight loss, or pathological changes in their livers, kidneys or lungs. However, there was moderate atrophy of the thymus cortex. THI is a small imidazole-containing compound with structural similarity to histamine and urocanic acid, both known to have immunosuppressive properties. It is a widely used food additive with no known long-term toxic effects at low dosage. Thus, THI could be a useful immunosuppressive agent.
Immunoperoxidase staining of samples of normal human retina and choroid was performed to demonstrate selected adhesion molecules in vivo. Intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen-3 (LFA-3) and endothelial leucocyte adhesion molecule-1 (ELAM-1) were expressed on retinal vascular endothelium and ICAM-1 and ELAM-1 in the region of the external limiting membrane. The very late antigen-2 (VLA-2) was found around the retinal ganglion cells and in the inner and outer fibre layers. The endothelium on the choriocapillaris showed moderate staining of ICAM-1, and slight staining of LFA-3 and ELAM-1. The presence of these molecules in this distribution strongly suggests they have an important role in the pathogenesis of immunologically mediated ocular conditions.
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