Phenotypical characterization of the cells invading pancreatic islets of diabetic BB/OK rats: effect of interleukin 2 receptor-targeted immunotherapy

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Abstract
We investigated immunohistochemically the phenotypes of mononucleated cells invading pancreatic islets of diabetic BB/OK rats in comparison to the diabetesresistant parental strain, and 12 and 120 days after a temporary treatment (10 days) with a monoclonal antibody (1 mg/kg b.w.) directed against interleukin 2 receptor (IL 2R) combined with a subtherapeutic dose of cyclosporin A (1.5 mg/kg b.w.). Using a panel of monoclonal antibodies (OX‐19, OX‐8, W3125, KI‐M2R, OX‐6, OX‐17, ART‐18) and the alkaline phosphatase anti‐alkaline phosphatase system to visualize the bound primary antibodies, we observed an even distribution of mono‐nucleated cells across the endocrine pancreas at a “background” level when obtained from diabetes‐resistant parental rat strain. Diabetic BB/OK rats, characterized by a moderate hyperglycemia and a marked decrease of pancreatic insulin content, displayed a remarkable accumulation of mononucleated cells in the endocrine pancreas. Morphometric studies revealed an increase of all phenotypes investigated, nearly all mononucleated cells expressed class I1 histocompatibility antigens (OX‐6+, OX‐17+) and the number of cells expressing the IL 2R (ART‐18+) was markedly enhanced. Sixty‐seven percent of the immunotherapeutically treated BB/OK rats normalized plasma glucose and enhanced pancreatic insulin content. The successfully treated animals are characterized by a decrease of cells invading pancreatic islets (OX‐19+, OX‐8+, W3/25+, KI‐M2R+), a decrease of class II histocompatibility antigen and IL 2R expression. The number of IL 2R cells is also diminished in the endocrine pancreas of unsuccessfully treated BB rats.