CTLA4 IG ON RENAL ALLOGRAFT SURVIVAL: TREATMENT DELAY & COMB W/ CYCLOSPORINE

本研究的目的是检验CTLA 4-IG在肿瘤细胞中表达的假设， 将延长非人灵长类动物模型中同种异体肾移植物的存活时间。 CTLA 4-IG已被证明可以改变同种异体移植物排斥反应， 产生延长的移植物存活和/或诱导特异性 在啮齿动物模型中无反应。 成年恒河猴（11.8-13.5 kg）用于这些研究。 10只动物接受了 同种异体肾移植，左肾切除，同时右肾切除 对侧输尿管结扎。 进行了配对移植 同时通过受体个体之间的肾脏交换。 每对中的一个受体用CTLA 4-IG处理，另一个受体用CTLA 4-Ig处理。 作为用人白蛋白处理的对照。 肾 对照治疗组中的同种异体移植物迅速失效（4-8天）， 组织学分析表明细胞和体液免疫 中介机制。 CTLA 4-IG治疗4例受者之一， 与同种异体移植物存活时间显著延长相关。 一 CTLA 4-IG治疗的受体继发于远端坏死而死亡 移植输尿管，未纳入分析。 总的来说， 该初步研究的结果表明，CTLA 4-IG具有 来延长灵长类动物肾移植存活时间

The aim of this study was to test the hypothesis that CTLA4-Ig will prolong survival of renal allografts in a nonhuman primate model. CTLA4-Ig has been shown to modify the allograft rejection response to produce prolonged graft survival and/or induce specific unresponsiveness in rodent models. Adult rhesus macaques (11.8-13.5 kg) were utilized for these studies. Ten animals received an allogeneic renal transplant, a left nephrectomy and simultaneous right contralateral ureter ligation. The paired transplants were performed simultaneously by exchange of kidneys between recipient individuals. One recipient in each pair was treated with CTLA4-Ig and the other served as a control being treated with human albumin. Renal allografts in the control treatment group promptly fail (4-8 days) and the histologic analysis suggests both a cellular and humoral immune mediated mechanism. CTLA4-Ig treatment in one of four recipients was associated with marked prolongation of allograft su rvival. One CTLA4-Ig treated recipient died secondary to necrosis of the distal transplant ureter and was not included in the analysis. In summary, the results of this pilot study suggest that CTLA4-Ig has the ability to prolong primate renal allograft survival.