title: Intravenous and portal venous administration of modified donor antigen prolongs rat parathyroid allograft survival.
abstract: The effect of pretransplant (day -6) systemic intravenous or portal venous immunization with modified donor antigen combined with cyclophosphamide treatment (75 mg/kg on day -4) on rat parathyroid allograft survival was evaluated. Systemic intravenous preimmunization of Buffalo recipients with 10(8) untreated Lewis donor spleen cells plus cyclophosphamide resulted in 100% accelerated rejection of Lewis parathyroid allografts (mean survival time, 7.3 +/- 0.9 days vs 10.8 +/- 1.1 days for controls). Portal venous administration of untreated cells plus cyclophosphamide reduced accelerated rejection to 40% but could not prolong graft survival (10.8 +/- 2.7 days). Intravenous or portal venous preimmunization with heat-inactivated cells (45 degrees C for 60 minutes) plus cyclophosphamide also did not prolong graft survival, with accelerated rejection occurring in 20% and 40% of recipients, respectively. In contrast, preimmunization by either route with ultraviolet B-irradiated cells (UVB; 12,000 joule/m2) plus cyclophosphamide significantly prolonged graft survival (intravenous = 22.2 +/- 6.0 days and portal venous = 21.4 +/- 7.2 days; p less than 0.005), with no accelerated rejection. Preimmunization with UVB cells combined with cyclophosphamide was synergistic, because neither treatment alone prolonged allograft survival (UVB cell preimmunization only = 10.8 +/- 1.3 days; cyclophosphamide only = 12.6 +/- 2.6 days). The effect of UVB preimmunization was donor specific because third-party Wistar-Furth UVB cells had no effect on Lewis graft survival (12.5 +/- 2.9 days). We conclude that pretreatment with UVB-modified donor antigen plus cyclophosphamide induces allospecific immune hyporesponsiveness and prolongs parathyroid allograft survival.
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, Mo 63110.
authors.forename: T
authors.initials: T
authors.lastname: Kamei
authors.forename: M P
authors.initials: MP
authors.lastname: Callery
authors.forename: M W
authors.initials: MW
authors.lastname: Flye
mesh_terms: D000818:Animals; D003520:Cyclophosphamide / Q000627:therapeutic use; D006084:Graft Rejection; D006085:Graft Survival; D007165:Immunosuppression Therapy; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D010280:Parathyroid Glands / Q000637:transplantation*; D011169:Portal Vein; D051381:Rats; D011915:Rats, Inbred BUF; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D013154:Spleen / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D003520:Cyclophosphamide