SURVIVAL OF RAT SMALL-BOWEL ALLOGRAFTS TREATED WITH ALLOTRAP 07(R)

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 07(R)), We wished to determ ine the efficacy of these peptides in the highly immunogenic ACI > LEW and LEW > ACI small bowel transplant models, Animals were divided int o 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 o n Days -19 to 4); VI, Allotrap + CsA (as in groups III and V); VII, Al lotrap + CsA (as in groups III and V, with Allotrap administered intra graft Days 0-4), The animals were sacrificed at the time of graft reje ction (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 cul ture (MLC) reactivity against self, donor, and third-party splenocytes was assessed, Statistical analysis was performed by ANOVA with Dunnet t's t for multiple comparisons against a control as a post hoc test. W e 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 comb ined CsA and Allotrap, but not with Allotrap alone. We conclude that A llotrap decreases response to alloantigens, and slightly, but signific antly prolongs graft survival in the highly immunogenic small bowel tr ansplant model. (C) 1997 Academic Press.