Transplantation of isolated islets of Langerhans in diabetic dogs. II. The influence of histocompatibility.

By means of collagenase digestion and the Ficoll gradient separation technique, viable islets of Langerhans could be isolated from dog pancreata. The isolated islets were capable of secreting insulin after glucose stimulation. These islets of Langerhans were transplanted into the livers of diabetic dogs. We transplanted islets isolated from I donor pancreas for 1 kg body wt of the recipients. The dogs were made diabetic by subtotal pancreatectomy (80%) and two injections of 25 mg streptozotocin/kg body wt. In our experiments, we selected donor-recipient pairs by means of the mixed lymphocyte reaction macrophage electrophoretic migration inhibition (MLR-EM) test. In the group with a depression in the MLR-EM test of more than 15% (strong histoincompatibility), the mean survival time of the transplanted dogs was 46 ± 16 days. Another group of recipients with a depression of macrophage migration of less than 8% (weak histocompatibility) had a mean survival time of 135 ± 49 days after intraportal islet transplantation, and the blood glucose values could be normalized in this group for a period of 70 days. We found significant differences between both the groups in the glucose tolerance tests and in the IRI concentrations in the portal vein and in the vena cava superior. In the recipients, which received weakly histoincompatible islets, the IRI concentration in the superior vena cava was 64% of the normal value in the vena cava superior 4 weeks after intrahepatic islet transplantation. By means of the MLR-EM test, we were able to correlate inhibition with signs of rejection of the transplanted islets. Our experiments demonstrated that an allogeneic islet transplantation in diabetic dogs across a weakly histocompatible barrier can improve the results in comparison to the islet transplantation across a strongly histocompatible barrier. However, this typing maneuver alone is not able to prevent the islet rejection.