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

本研究的目的是检验 CTLA4-Ig 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。 CTLA4-Ig 已被证明可以改变同种异体移植排斥反应 产生延长的移植物存活和/或诱导特异性 啮齿动物模型反应迟钝。 成年恒河猴（11.8-13.5 kg）用于这些研究。 十只动物接受了 同种异体肾移植，左肾切除术和同时右肾切除术 对侧输尿管结扎。 进行了配对移植 同时通过接受者个体之间交换肾脏。 每对中的一名接受者接受 CTLA4-Ig 治疗，另一名接受者接受 CTLA4-Ig 治疗。 作为用人白蛋白处理的对照。 肾 对照治疗组的同种异体移植很快就失败了（4-8天）并且 组织学分析表明细胞和体液免疫 介导机制。 四名接受者之一的 CTLA4-Ig 治疗是 与同种异体移植物存活的显着延长有关。 一 CTLA4-Ig 治疗的受者因远端坏死继发死亡 移植输尿管，未包含在分析中。 总而言之， 该初步研究的结果表明 CTLA4-Ig 具有 延长灵长类同种异体肾移植物的存活率。

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.