Survival of rat small bowel allografts treated with allotrap 07R.
Previous reports from other investigators demonstrate prolongation of allogeneic heart graft survival and decrease in CTL responses in rats treated with a small synthetic peptide corresponding to residues 75-84 of the human HLA-B7-01 molecule (Allotrap 07R). We wished to determine the efficacy of these peptides in the highly immunogenic ACI > LEW and LEW > ACI small bowel transplant models. Animals were divided into treatment groups: I, none; II, Allotrap (20 mg/kg/day on Days 0-4); III, cyclosporine (CsA; 10 mg/kg/day on Days 0-4); IV, Allotrap + CsA (as in groups II and III); V, Allotrap (40 mg/kg/day every other day on Days -19 to 4); VI, Allotrap + CsA (as in groups III and V); VII, Allotrap + CsA (as in groups III and V, with Allotrap administered intragraft Days 0-4). The animals were sacrificed at the time of graft rejection (defined by dusky, necrotic stoma and increased stomal output). Peripheral blood, spleen, native bowel, and allograft intraepithelial and lamina propria lymphocytes were harvested and mixed lymphocyte culture (MLC) reactivity against self, donor, and third-party splenocytes was assessed. Statistical analysis was performed by ANOVA with Dunnett's t for multiple comparisons against a control as a post hoc test. We found a very slight, but significant prolongation of graft survival in with treatment protocol V for both strain combinations. In addition, MLC response of splenocytes to donor antigen was decreased with combined CsA and Allotrap, but not with Allotrap alone. We conclude that Allotrap decreases response to alloantigens, and slightly, but significantly prolongs graft survival in the hihgly immunogenic small bowel transplant model.
Tice
D G
DG
Department of Surgery, State University of New York Health Science Center at Syracuse 13210, USA.
Bruch
D
D
Buelow
R
R
Squiers
E C
EC
D000818:Animals; D006084:Graft Rejection / Q000188:drug therapy; D006085:Graft Survival / Q000187:drug effects*; D015395:Histocompatibility Antigens Class I / Q000494:pharmacology; D007421:Intestine, Small / Q000637:transplantation*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous
D015395:Histocompatibility Antigens Class I; D010455:Peptides; C092373:allotrap