Donor-specific unresponsiveness induced by intraportal grafting and FK506 in rat islet allografts: importance of low temperature culture and transplant site on induction and maintenance.

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 degrees C, 7 days) islets were used for initial transplantation in conjunction with FK506, 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.(ABSTRACT TRUNCATED AT 250 WORDS)