HISTOCOMPATIBILITY DIFFERENCES AND CARDIAC TRANSPLANT TOLERANCE PRODUCED BY INTRATHYMIC PRETREATMENT

Control of cardiac transplant rejection without toxic immunosuppressiv e drugs remains an unreached goal. Our laboratory and others have show n that intrathymic inoculation of donor-specific allogeneic spleen cel ls can produce tolerance to a subsequent cardiac allograft. The presen t experiments were designed to investigate whether the degree of donor -recipient histoincompatibility influenced the efficacy of this techni que. Four congeneic strains of rats with different degrees of histoinc ompatibility were studied. Heterotopic cardiac transplantation was don e with the following congeneic strain combinations: DA donor into PVG recipient (full major histocompatibility complex and nonmajor histocom patibility complex incompatibility); PVG.RT1a donor into PVG recipient (full major histocompatibility complex incompatibility); PVG.RT1a don or into PVG.R1 recipient (partial major histocompatibility complex inc ompatibility). Prospective graft recipients underwent intraperitoneal injection of 1 mi antilymphocyte serum and intrathymic injection of 5 x 10(7) prospective donor spleen cells. Three weeks later, heterotopic cardiac transplantation was done with a heart from a donor of the sam e strain as that used to obtain splenocytes for intrathymic injection. Prolongation of graft survival was observed in pretreated recipients in all strain combinations but was greatest in recipients that differe d from donors at fewer histocompatibility loci. Complete graft toleran ce was not seen in strain combinations that included nonmajor histocom patibility complex incompatibilities. DA heart survival in PVG recipie nts was 50.6 days (p < 0.04 versus controls); PVG.RT1a graft survival in PVG hosts was 165.8 days (p < 0.02 versus control) and in PVG.R1 re cipients 163.8 days (p < 0.02 versus controls) with four of five graft s in each group surviving indefinitely (more than 200 days).