The Previous Study Of Clinical Apllication Of Inducing Tolerance To Rat Cardiac Allografts

Background:Organ transplantation is still the only effective therapy for treating patients with end-stage heart diseases. It is generally agreed that intrathymic(IT) injection of alloantigens is effective on inducing donor-specific tolerance to cardiac allograft. The induction of donor-specific tolerance could prevent the patient from the side effects of using immunosuppressive drugs. We have recently investigated the feasibility of applying such approach in swine and the results are inspiring. However,the production tolerance requires a time-lag between intrathymic pretreatment and transplantation,it is not beneficial to cadaveric organ transplantation.Purpose:This study was designed to investigate the production of tolerance to cardiac allografts by combining intrathymic inoculation with allogeneic antigen at the day of transplantation with usage of immunosuppressive drugs for short time.Methods:2.5 X 107 allogeneic spleen cells of SD rats were intrathymically injected into Wistar rats at the time of cardiac allografting from SD rats with short-course therapy of FK506 in our experimental group. In control group,2.5 X 107 allogeneic spleen cells(Sc) of SD rats were intrathymically injected into Wistar rats at the time of cardiac allografting from SD rats without short-course therapy of FK506.Survival time of cardiac allografts,interleukin(IL-2 and IL-10) in recipients serum,the mixed lymphocyte reaction(MLR) between donors and recipients and the histological changes in SD cardiac allografts were investigated.Results:The mean survival time(MST) of cardiac allografts from SD rats in Wistar recipients without pretreatment was 6.8+1.9 days. Pretreatment of combining IT injection of SD spleen cells with usage of could prolong graft survival (MST 55.0 + 24.7 days) in recipients. In control group,allogeneic IT injection alone on the grafting day failed to induce tolerance (MST 17.4 + 5.1 days). The results of MLR showed that spleen T cells harvested from tolerant Wistar rats displayed hyporesponsiveness against naive SD spleen cells(P<0.05),and the proliferous responses of no pretreatment group were greater than those in the tolerant rats(P<0.05). Cytokine expression of IL-10 in no pretreatment group was similar to that in naive Wistar rats. In the tolerant rats,expression of IL-10 was down-regulated on day 7 after grafting;IL-10 was strongly expressed(P<0.05) on day 25 after grafting;expression of IL-10 was decreased though it was higher than that in naive Wistar rats on day 50 after grafting. The level expression of IL-2 was higher before the grafts rejected than that after grafts rejected in no treatment group (P<0.05). In the tolerant rats,expression of IL-2 was not greater than those in the naive Wistar rats(P>0.05).Conclusion:Perfect donor-specific tolerance was obtained identically by intrathymical injection of donor spleen cells and short course of usage of post-grafting on the day of transplantation. The level of IL-2 might be referable to occurrence of acute rejection and what of IL-10 might be relative to immune tolerance.