CTLA4 IG RENAL ALLOGRAFT SURVIVAL:MAINTENANCE TRTMENT:CYCLOSPORINE & PREDNISONE

对破坏移植的免疫反应的最佳抑制 器官在临床移植中的应用尚未实现。因此， 接受移植的患者继续面临着 移植的排斥反应以及移植的副作用 非特异性免疫抑制策略，需要 维持这些移植，包括增加的发病率 包括感染和恶性肿瘤。T淋巴细胞发挥着重要的作用 在移植排斥反应中的作用。B7/CD28信号通路已经被 被证明对有效的T细胞激活很重要。上一首 对啮齿动物模型的研究表明，阻断这一机制 使用CTLA4-Ig试剂可以有效地延长 移植器官的存活。这项研究的目的是测试 CTLA4-Ig延长肾脏存活的假说 在非人类灵长类动物模型中进行移植。这一点的证明 效果将有助于本试剂的应用，以防止 临床移植中的移植物排斥反应。肾移植是 在恒河猴身上进行，以测试3种特异性CTLA4-Ig治疗 协议。1)移植时单独启动CTLA4-Ig；2) 移植后2天单独启动CTLA4-Ig；3)CTLA4-Ig 联合环孢素和泼尼松时开始使用 移植。到目前为止的结果表明，短期的 移植时仅接受CTLA4-Ig治疗与 四位受者中有一位的同种异体移植物存活显著延长。 推迟CTLA4-Ig治疗的开始似乎没有 提高存活率。CTLA4-Ig联合CTLA4-Ig 16天疗程 环孢素和泼尼松延长移植肾存活时间但不能 无限期的。将这三重免疫抑制疗法扩展到 移植后13周与存活率的增加有关。在……里面 综述：CTLA4-Ig在非人灵长类动物肾脏中具有免疫抑制作用 同种异体移植模型。

Optimal inhibition of the immune response to destroy transplanted organs in clinical transplantation has yet to be achieved. Therefore, transplant recipient patients continue to experience problems with rejection of their transplants as well as the side effects of the non-specific immunosuppressive strategies which are required to maintain these transplants which include an increased incidence of both infections and malignancies. T lymphocytes play an important role in transplant rejection. The B7/CD28 signaling pathway has been shown to be important for effective T cell activation. Previous studies in rodent models have demonstrated that blockade of this pathway with a reagent called CTLA4-Ig can effectively prolong the survival of transplanted organs. The aim of this study was to test the hypothesis that CTLA4-Ig will prolong the survival of renal transplants in a nonhuman primate model. The demonstration of this effect would facilitate the application of this reagen t to prevent graft rejection in clinical transplantation. Renal transplants were performed in rhesus macaques to test 3 specific CTLA4-Ig treatment protocols. 1) CTLA4-Ig alone initiated at the time of transplant; 2) CTLA4-Ig alone initiated 2 days after transplant; and 3) CTLA4-Ig combined with cyclosporine and prednisone initiated at the time of transplants. The results to date indicate that a short course of CTLA4-Ig treatment alone at the time of transplant was associated with marked prolongation of allograft survival in one of four recipients. Delaying the initiation of CTLA4-Ig treatment did not appear to improve survival. A 16-day course of CTLA4-Ig combined with cyclosporine and prednisone prolonged renal allograft survival but not indefinitely. Extension of this triple immunosuppressive therapy to 13 weeks after transplant was associated with increased survival. In summary, CTLA4-Ig is immunosuppressive in the nonhuman primate renal allograft model.