Phenotypical characterization of the cells invading pancreatic islets of diabetic BB/OK rats: effect of interleukin 2 receptor-targeted immunotherapy.
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.
Hahn
H J
HJ
Central Institute of Diabetes G. Katsch, Karlsburg, FRG.
Gerdes
J
J
Lucke
S
S
Liepe
L
L
Kauert
C
C
Volk
H D
HD
Wacker
H H
HH
Brocke
S
S
Stein
H
H
Diamantstein
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D007167:Immunotherapy; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000145:classification / Q000473:pathology; D051381:Rats; D011922:Rats, Mutant Strains; D015375:Receptors, Interleukin-2 / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007328:Insulin; D015375:Receptors, Interleukin-2