Effect of anti-Ia antibodies, culture, and cyclosporin on prolongation of canine islet allograft survival.
Evidence in rodents suggests that islet pretreatment to reduce islet immunogenicity will also require some form of immunosuppression of the recipient for islet allograft acceptance in highly reactive donor-recipient pairs. We attempted to ascertain whether outbred dogs would also require treatment of both donor islets and the recipient to prolong islet allograft survival. Untreated canine islets are uniformly rejected in 6-10 days in beagles. Tissue culture alone, at 37 degrees C for 7 days, or treatment of freshly prepared islets with anti-Ia monoclonal antibodies (MoAbs) (B1F6 + 7.2) did not prolong canine islet allograft survival. Treatment of culture-maintained canine islets with anti-Ia MoAbs plus complement resulted in prolongation of islet allograft survival for 188 and 368 days in two of seven pancreatectomized nonimmunosuppressed beagles. The administration of low doses of cyclosporin A (CsA) intramuscularly, to recipients of untreated canine islet allografts had no effect on graft survival. By contrast, six of nine CsA-treated recipients of islets that were also treated with anti-Ia MoAbs (B1F6 + 7.2) plus complement showed prolongation of graft survival. Euglycemia was sustained for 19, 34, 89, and 300 days after the CsA was discontinued (day 30) in four of these animals. Two animals had unstable grafts from the beginning that failed 23 and 29 days after transplantation. Our results indicate that simple maneuvers like short-term tissue culture at 37 degrees C and treatment of freshly isolated islets with anti-Ia MoAbs and complement are inadequate to prevent rejection in outbred pancreatectomized beagles.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001786:Blood Glucose / Q000032:analysis; D003524:Cyclosporins / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006085:Graft Survival / Q000187:drug effects*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007515:Islets of Langerhans / Q000187:drug effects / Q000276:immunology; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009924:Organ Culture Techniques; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D001786:Blood Glucose; D003524:Cyclosporins; D000949:Histocompatibility Antigens Class II