title: 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.
authors.affiliation: Department of Surgery, University of Chicago, IL 60637.
authors.forename: D M
authors.initials: DM
authors.lastname: Lloyd
authors.forename: S J
authors.initials: SJ
authors.lastname: Cotler
authors.forename: A G
authors.initials: AG
authors.lastname: Letai
authors.forename: F P
authors.initials: FP
authors.lastname: Stuart
authors.forename: J R
authors.initials: JR
authors.lastname: Thistlethwaite
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology; D010179:Pancreas / Q000276:immunology; D016035:Pancreas Transplantation; D010477:Perfusion; D051381:Rats; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II