Experimental study for the clinical application of discordant cardiac xenograft.

首先，我们使用抗补体药物FUT175和K76C00H修饰受体补体(C)系统，特别是替代途径，并使用豚鼠对大鼠和猪对狗不协调心脏异种移植模型，评估这些药物对超急性排斥反应的影响。FUT175和K76在豚鼠到大鼠模型中均能延长移植物的存活时间，但在猪到狗模型中被强天然抗体所抵消。接下来，从移植物侧修饰的角度，我们研究了CD55或CD59掺入的异种红细胞(E)对人补体的敏感性。CD55/ cd59介导的对人C异种细胞的保护作用在e -物种之间存在差异。在这两个C通路中，在C3和后期阶段，合并CD55对e -猪或e -羊的保护都比CD59更有效。除了C系统引起超急性异种移植排斥反应外，抗体反应和细胞介导的免疫反应在密切相关的物种组合中也起着重要作用，例如大鼠对小鼠。我们还研究了其排斥机制。我们的研究结果表明，体内用抗cd4但抗cd8或抗c受体抗体治疗可延长移植物的存活时间。CD4 T细胞不仅具有辅助功能，而且在大鼠对小鼠异种移植物的加速排斥反应中起着至关重要的作用。

At first, we modified the recipient complement(C) system, especially the alternative pathway, with the anti-complement drug, FUT175 and K76C00H, and evaluated the effects of these drugs in the hyperacute rejection, using guinea-pig to rat and pig to dog discordant cardiac xenograft model. The administration of both FUT175 and K76 resulted in the prolongation of the graft survival in guinea pig to rat model,but the effects of these drugs were abolished by strong natural antibody in pig to dog model. Next, from the point of the modification in the graft side, we investigated the susceptibility to human complement of xeno-erythrocytes (E) in which CD55 or CD59 was incorporated. The efficacy of CD55/CD59-mediated protection of xenogeneic cell from human C differed among the E-species. In both C pathways, E-swine or E-sheep were protected by the incorporated CD55 more effectively than CD59 at both C3 andlate steps. Apart from C system which causes hyperacute xenograft rejection, the antibody response and the cell-mediated immune responses have a important role, in the closely related species combination, such as rat to mouse. We also investigated its rejection mechanism. Our results showed that in vivo treatment with anti-CD4 but anti-CD8 or anti-C receptor antibody lead to a prolongation of graft survival. CD4 T cells are of crucial importance, not only in helper function, but also in the effector phase in the accelerated rejection of rat to mouse xenograft.