Demonstration of donor specific unresponsiveness in rat islet allografts: importance of transplant site for induction by cyclosporin A and maintenance

Abstract

The purpose of the present study was to evaluate the effects of transplant site (the liver via the portal vein vs the renal subcapsular space) on islet allograft survival using cyclosporin A and also to determine whether or not the unresponsiveness obtained is donor specific and how the site selected is related to the maintenance of unresponsiveness. Prolongation of islet allograft survival (WKA/Qdj:RT1u----Lewis:RT1l) was obtained by using hand-picked clean fresh islets as donors and by s.c. administration of cyclosporin A (30 mg/kg, day 0, 1, 2) when the islets were transplanted into the liver. Eleven out of 15 recipients were normoglycaemic for more than 90 days after transplantation (control mean survival time: 4.4 +/- 1.1 days, n = 5). However, all the renal subcapsular grafts were rejected within 18 days after transplantation. Two normoglycaemic recipients bearing intrahepatic grafts were challenged with full-thickness donor-strain (WKA/Qdj) skin grafts at 120 days after the islet transplantation. Both recipients became diabetic and the skin grafts rejected within 16 days. The nine normoglycaemic recipients were made diabetic again with streptozotocin (40 mg/kg) between 90 and 120 days after the initial islet transplantation. Re-transplants of fresh donor-strain (WKA/Qdj) islets into the liver (n = 3) in the absence of cyclosporin A maintained normoglycaemia in the recipients for more than 60 days, whereas re-transplants of donor-strain islets beneath the kidney capsule were rejected within 20 days. Intrahepatic re-transplants of third party grafts (PVG/c: RTlc) (n = 3) were rejected after seven days.(ABSTRACT TRUNCATED AT 250 WORDS)