A COMPOSITE GRAFT OF ISLET PLUS DONOR LYMPH NODE CELLS COULD NOT INDUCE DONOR SPECIFIC TOLERANCE IN A "LOW RESPONDER" RAT COMBINATION WITH CLASS I MHC DISPARITY

Abstract

408 We previously reported that WF(RT1U) pancreas transplantation, but not islet transplantation protected recurrence of IDDM by anti-ICAM-1/LFA-1 mAbs in diabetic prone BB rats (RT1U). We have recently reported that class I MHC disparate PVG.R1 (RT1.A'B'D'C') pancreaticoduodenal grafts could be rejected in diabetic PVG (RT1.A'B'D'C') recipients by streptozotocin, while PVG.R1 liver, heart, and kidney grafts could survive indefinitely without immunosuppression. Purpose: This study was to examine that passenger leukocytes have a potencial to induce donor specific tolerance or not, in this "low responder" combination with MHC class I disparity. Materials and Methods: PTx was performed using a modification of S. Lee's method. Approximately overnight cultured 1500 islets were implanted into the subcapsular space of left kidney. Rejection was confirmed by hyperglycemic relapse over 300 mg/dl and by histological examination. PVG recipients were divided into the following 6 groups. Mixed lymphocyte reaction (MLR) and limiting dilution assay to estimate frequencies of IL-2 producing helper (fThp) and cytotoxic (fTcp) T cell precursors to PVG.R1 alloantigens were adopted for cellular immuity.□Flow cytometoric analysis (FACS) to detect antidonor antibodies was performed. Results: Only one case was rejected within 57 days in PTx (n=7) and 3 cases were rejected in ITx (n=7) within 26, 20, 19 days post grafting. Tolerant rats which PTx or ITx grafts survived more than 100 days, were challenged with donor (R1) and 3rd party (BUF) skin grafts to examine the alloantigen specificity. PTx rats rejected BUF skin grafts within 15 days, but interestingly accepted R1 skin (>100 days). Tolerant ITx rats (group 2) rejected both R1 and BUF skin grafts in 13 and 10 days, respectively. Tolerant ITx rats□(group 3.4) transplanted copmosite graft of islet plus with donor R1 ileoceacal lymph node cells, however, are prolonged only donor R1 skin than ITx (group 2). Tolerant ITx rats (group 5) transplanted copmosite graft of islet plus with BUF ileoceacal lymph node cells, however, are prolonged only donor R1 skin than ITx (group 2). Tolerant ITx rats (group 6) transplanted copmosite graft OF islet plus R1 spleen cells, however, are prolonged only donor R1 skin but could not induced tolerance. Conclusion: Donor specific tolerance was obtained by PTx, but not ITx. Immunoreguratory passenger leukocytes might be necessary for the induction of tolerance in ITx in this combination. It was not necessary for donor ileocecal lymph node to prolong graft survivals. (Table)Table