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

Abstract

We investigated immunohistochemically the phenotypes of mononucleated cells invading pancreatic islets of diabetic BB/OK rats in comparison to the diabetes-resistant 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, W3/25, 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 mononucleated 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 II 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.

• Authors: H J Hahn, J Gerdes, S Lucke, L Liepe, C Kauert, H D Volk, H H Wacker, S Brocke, H Stein, T Diamantstein
• Journal: European journal of immunology (Eur J Immunol) Vol. 18 Issue 12 Pg. 2037-42 (Dec 1988) ISSN: 0014-2980 [Print] Germany
• PMID: 3065088 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Insulin
• Receptors, Interleukin-2

Topics

• Animals
• Antibodies, Monoclonal (therapeutic use)
• Diabetes Mellitus, Experimental (immunology, pathology, therapy)
• Immunotherapy
• Insulin (metabolism)
• Islets of Langerhans (immunology, pathology)
• Leukocytes, Mononuclear (classification, pathology)
• Rats
• Rats, Mutant Strains
• Receptors, Interleukin-2 (immunology)