PROLONGED SURVIVAL OF ALLOTRANSPLANTED ISLET OF LANGERHANS CELLS IN THE RAT

Abstract
Male Lewis strain rats (250-300 g) rendered diabetic (hyperglycemic-glycosuric) by i.v. injection of 65 mg/kg of streptozotozin were used as recipients. The rats were transplanted 4-6 wk after streptozotocin treatment. Only rats with blood glucose levels over 400 mg/100 ml on the day before transplantation were used. Wistar-Furth rats (150-250 g) served as donors. Islets from 4 donors were pooled for each recipient and injected into the portal vein. Liver extracts from Wistar-Furth rats were prepared according to the method of Medawar and Brent and stored at -70.degree. C. The extracts were derived from an initial concentration of 500 mg wet weight of liver/ml. The supernatant fluids from phase I Bordetella pertussis cultures which were used, induced a leukocytosis of 100,000 cells/mm3 3 days after the injection of 1 ml i.p. A commercial preparation of rabbit anti-rat lymphocyte serum (ALS) and prednisolone were used. The combination of pretreatment with donor liver extract and pertussis, followed by a short course of ALS treatment, resulted in a much better overall survival of functioning islets of Langerhans allotransplants than with the other forms of immunosuppression tested.