Pancreas-Graft Immunogenicity and Pretreatment With Anti-Class II Monoclonal Antibodies

Abstract

Pretreatment of organ allografts to reduce graft immunogenicity is an attractive and potentially clinically applicable concept. We have studied the effect of perfusing rat pancreases with anti-class II monoclonal antibody (MoAb), to remove class II- positive accessory cells from the intact organ, on prolongation of allograft survival after transplantation. The capacity of pancreatic islets obtained from these perfused organs to stimulate proliferation of allogeneic T-lymphocytes was studied in a mixed islet-lymphocyte culture (MILC). There was a significant prolongation in pancreas-allograft survival when intact pancreases were transplanted after a 3-h normothermic perfusion with MoAb reactive with class II antigens (16.2 +/- 3.6 days, n = 19) compared with control animals (11.0 +/- 1.4 days, n = 24). In vitro treatment of islets with MoAb and complement (CI) inhibited their stimulatory capacity in the MILC, as measured by [3H]thymidine uptake. Similarly, the stimulatory capacity of islets removed from perfused pancreases was also abrogated when MoAb was included in the perfusate. Although reduction in graft immunogenicity, by increasing allograft survival, was achieved by a 3-h pretreatment regimen, it was not sufficient to inhibit rejection altogether in our transplant model.

Ex vivo perfusion of canine pancreaticoduodenal allografts using class-II-specific monoclonal antibody delays the onset of acute rejection

“…Murine islets treated with DC-specific MoAb and complement were shown to survive for over 200 days [ 6]. Normothermic perfusion of rat pancreas allografts with class-11-specific MoAb using a perfusion circuit was demonstrated to pro- [9). The mechanism of these beneficial effects with pretreatment using class-11specific MoAb has been suggested: when DCs combine with MoAb, they would lose their APC function in pancreas allografts, and T-cell sensitization from alloantigens could not be carried out.…”

“…Manipulation of allografts to modulate their antigenicity might be an attractive and potentially clinically applicable strategy as an alternative to current immunosuppression techniques. Pretreatment of the pancreas or islet allografts using class-11-specific monoclonal antibodies (MoAbs) was shown to result in prolongation of graft survival in rodent models [6,9] but was ineffective in canine models [2,15]. The following experiments were designed to determine whether or not ex vivo perfusion of canine pancreaticoduodenal allografts using class-II-specific MoAb could delay the onset of acute rejection.…”