CELLULAR BASIS FOR DISCORDANT XENOGRAFT REJECTION

用于移植的尸体捐赠器官短缺，许多人 患者无限期地接受透析，甚至在等待其他治疗时死亡。 器官移植尸体捐献者的数量显著增加， 预期不会进行同种异体移植。异种移植是一种潜在的 解决方案，但拒绝响应更难挫败。 使用一致性（非人灵长类动物）供体的临床尝试已经 短暂的成功，但大规模的应用将需要使用 不和谐的物种。 天然（NA）和补体抗体（C）导致超急性排斥反应 (HAR)但这可以通过NA和C的耗竭来防止。然而，尽管如此， 长期功能难以实现。我们建议研究 HAR大鼠对猪心的细胞排斥反应 防止NA和C耗尽。预防或延迟之间的窗口 HAR排斥反应将用于识别免疫细胞亚群， 渗入异种移植物我们将利用这些信息， 针对亚群的靶向特异性免疫抑制策略。我们也 将决定免疫球蛋白抗体重新出现的动力学 通过各种亚型的过继转移。这项工作应该允许 排斥反应中细胞反应与体液反应的关系 不协调异种移植物的建立，并可能导致发展 特异性免疫抑制策略来预防异种移植排斥反应。

There is a shortage of cadaver donor organs for transplantation, and many patients remain indefinitely on dialysis or even die waiting for other organ transplants. A significant increase in cadaver donors for allografts is not anticipated. Xenotransplantation is a potential solution, but the rejection response is more difficult to thwart. Clinical attempts with concordant (non-human primates) donors have had transient success, but large scale application would necessitate the use of discordant species. Natural (NA) and antibodies complement (C) lead to hyperacute rejection (HAR), but this can be prevented by NA and C depletion. Nevertheless, long-term function is difficult to achieve. We propose to study the cellular rejection response to the pig hearts in rats in whom HAR was prevented by NA and C depletion. The window between prevention or delay of HAR rejection will be used to identify the immune cell subsets that infiltrate the xenograft. We will then use this information to then target specific immunosuppressive strategies against the subsets. We also will determine the kinetics by which immunoglobulin antibodies reappear by adoptive transfers of various subsets. This work should allow the relationship between the cellular and the humoral responses in rejection of a discordant xenograft to be established, and may lead to development of specific immunosuppressive strategies to prevent xenograft rejection.