Abstract
Previously we demonstrated prolongation of islet allograft survival in rat by administration of FK506 to the recipients. The purpose of the present study was to determine whether specific immune unresponsiveness had been induced and to determine the effects of low temperature culture of donor islets as well as the transplant site on the induction of immune unresponsiveness. At 90 days after transplantation, normoglycemic recipients bearing functional intrahepatic grafts were made diabetic again with streptozotocin (STZ) and donor specific or third party islets were transplanted either into the liver or beneath the kidney capsule. When fresh islets were used as donors in initial transplantation in conjunction with FK506, intrahepatic re-transplants of fresh islets from the donor-specific strain in the absence of FK506 maintained normoglycemia for more than 60 days, while third party transplants (n = 3) were rejected within 1 wk. In contrast to intrahepatic regrafts, all the renal subcapsular regrafts from the donor-specific strain (n = 3) were rejected with mean survival time of 12.7 ± 6.4 days. When cultured (24°C, 7 days) islets were used for initial transplantation in conjunction with FKS06, re-transplants of fresh or cultured islets from the donor specific strain beneath the kidney capsule maintained normoglycemic in 3 out of 6 or all (n = 4) of the recipients, respectively. Cultured third party regrafts beneath the kidney capsule (n = 2) were rejected at 9 days. These findings clearly demonstrate that immune unresponsiveness induced by intraportal grafting of islets in conjunction with FK506 was donor specific and indicate that cultured islets appear more tolerogenic when used at the initial transplant and less immunogenic when used as regrafts. The present study also indicates the importance of transplant site in induction and maintenance of donor specific unresponsiveness.
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