Development of new immunosuppressive methods for organ transplantation targetting recognition of antigen and adhesive molecule

1.同种异体心脏移植（1）在术前短期给予大鼠抗α β TCR的mAb，可完全防止同种异体心脏移植的排斥反应。在处理的大鼠中诱导供体对心脏组织的特异性无反应性。(2)在排斥模型中，TNF α、IFN γ和IL-1 β细胞因子mRNA在排斥同种异体心脏移植物的组织中表达，但在治疗的同种异体心脏移植物中不表达。(3)用抗粘附分子CD 2的mAb短期治疗大鼠完全防止了心脏同种异体移植物的排斥反应。这种免疫抑制是供体特异性的，并由无活力维持。同种异体肺移植术同种异体肺移植术后第6天发生完全排斥反应。用抗α β TCR的单克隆抗体治疗大鼠可以延迟排斥反应的开始。但经处理的肺移植物在第9天出现排斥反应。肺和心脏抗原性的差异可能有助于存活.异种心脏移植在小鼠到大鼠的异种心脏移植模型中，移植物存活时间延长。应用抗α β TCR单克隆抗体、15-脱氧精胍菌素和术后脾切除，我们发现异种心脏移植物存活70天。

1. Allogeneic cardiac transplantation(1) Short-term preoperative treatment of rats with a mAb against alpha betaTCR completely prevented the rejection of cardiac allografts. The donor specific unresponsiveness to cardiac tissue was induced in treated rats.(2) In rejected models, TNFalpha, IFNgamma and IL-1beta cytokine m-RNA were expressed in the tissue from the rejecting allogeneic cardiac grafts but not in the treated allogeneic cardiac grafts.(3) Short-term treatment of rats with a mAb against adhesion molecule CD2 completely prevented the rejection of cardiac allografts. This immunosuppression was donor specific and maintained by anergy.2. Allogencic lung transplantationAllogeneic lung grafts were completery rejected on the 6th days. Treatment of rats with a mAb against alpha betaTCR delayd the beginning of rejection. But the treated lung grafts were rejected on the 9th days. The differentiation of antigenicity between lung and heart seemed to contribute to the survival.3. Xenogeneic cardiac transplantationIn the xenogeneic transplantation model of mouse to rat, we got the prolongation of graft survival. Using mAb against alpha betaTCR,15-deoxyspergualin and post-operative splenectomy, we found that xenogeneic cardiac graft survived 70 days.