Failure of nonimmunogenic islet allografts to induce donor-specific immunological unresponsiveness [corrected].
Highly purified perinatal rat islets, isolated by a nonenzymic in vitro culture technique, have been successfully transplanted across complete MHC barriers without immunosuppression. Acceptance of these allogeneically transplanted islets is hypothesized to result from an absence of antigen presenting cells (APCs) within the islets. This study was designed to examine the effects of organ transplantation and cyclosporine (CsA) therapy on the development of immunological unresponsiveness in recipients receiving a graft of culture-isolated islets. Kidneys were successfully allotransplanted into unilaterally nephrectomized rats, across a complete MHC barrier (Rt1lv1 to Rt1u) using CsA therapy initiated on the day of transplantation (7.5 mg/kg, orally for 14 days). Remaining native kidneys were removed 14 days following renal allotransplantation. Limited mononuclear cell (MNC) infiltrates were observed in biopsies of renal allografts, taken 30 days posttransplant, but failure of the renal allograft was not observed. Animals bearing established renal allografts (n = 10) received allografts of approximately 200 highly purified perinatal islets (ACl, n = 5; F-344, n = 5), transplanted to the kidney subcapsule of the established renal allograft at least 30 days following renal allotransplantation (at least 16 days following termination of CsA). Islet allografts were not rejected, and, as expected, did not initiate rejection of the renal allograft. Similar results were observed in renal allograft recipients rendered diabetic by a single injection of streptozotocin (STZ, 65 mg/kg, n = 5) and receiving islet allografts of sufficient mass (approximately 1200-1400 islets) to reverse STZ-induced hyperglycemia. Further, neither islet nor renal allografts were rejected following challenge by 1 x 10(7) donor-strain dendritic cells (DCs).(ABSTRACT TRUNCATED AT 250 WORDS)
Dept. of Pediatrics, Division of Endocrinology, University of Kansas Medical Center, Kansas City, 66160-7330.
R J
RJ
Ketchum
C
C
Moyer
H C
HC
Su
W V
WV
Moore
D000818:Animals; D000831:Animals, Newborn; D016572:Cyclosporine / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000601:surgery*; D006650:Histocompatibility Testing; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D051381:Rats; D011912:Rats, Inbred ACI; D011916:Rats, Inbred F344; D011920:Rats, Inbred WF; D014184:Transplantation, Homologous / Q000276:immunology*
D016572:Cyclosporine