Ghebremariam Yohannes T, Smith Scott A, Anderson J B, Kahn D, Kotwal Girish J
Division of Medical Virology, IIDMM, University of Cape Town 7925, HSC, Cape Town, South Africa.
Ann N Y Acad Sci. 2005 Nov;1056:123-43. doi: 10.1196/annals.1352.028.
Xenotransplantation, the transplantation of cells, tissues, and/or organs across species, has proven to be an enormous challenge, resulting in only limited achievements over the last century. Unlike allotransplantation, the immunologic barriers involved in xenotransplant rejection are aggressive and usually occur within minutes in a hyperacute fashion. The use of organs from phylogenetically related concordant species may not be practical. Discordant xenotransplantation is characterized by hyperacute graft rejection, and to use nonprimate discordant organs for human benefit will require manipulation of the taxonomic differences. The hyperacute rejection process is primarily due to the attachment of preformed xenoreactive antibodies to the donor vascular endothelium, which results in hyperactivation of the complement system beyond the control of the natural complement regulatory proteins. Understanding the complex and diverse immune components involved in hyperacute, acute, and accelerated rejections has resulted in the development of different hematologic and molecular strategies. Plasmapheresis has been used to remove xenoantibodies, and xenoperfusion techniques are used to create a suitable and familiar environment for the xenograft. Various molecular approaches, such as the development of transgenic animals expressing human complement regulatory proteins such as CD59 or decay accelerating factor (DAF), to downregulate complement activation or the production of pigs lacking the xenoreactive antigen by knockout of the Gal alpha-1,3-galactosyl transferase gene have also been attempted. A combination of these techniques together with the administration of soluble complement inhibitors such as the vaccinia virus complement control protein (VCP) may well contribute to prolong graft survival. However, various issues including the possible emergence of new viral infections have confounded the topic of xenotransplantation. Here the different modulatory approaches and agents mediating interventions in xenorejection are discussed.
异种移植，即将细胞、组织和/或器官跨物种移植，已被证明是一项巨大的挑战，在上个世纪仅取得了有限的成果。与同种异体移植不同，异种移植排斥反应中涉及的免疫屏障具有侵袭性，通常在数分钟内以超急性方式发生。使用来自系统发育相关的协调性物种的器官可能并不实际。非协调性异种移植的特征是超急性移植物排斥反应，要将非灵长类非协调性器官用于人类则需要处理分类学上的差异。超急性排斥反应过程主要是由于预先形成的异种反应性抗体附着于供体血管内皮，导致补体系统过度激活，超出了天然补体调节蛋白的控制范围。了解参与超急性、急性和加速性排斥反应的复杂多样的免疫成分，促成了不同血液学和分子策略的发展。血浆置换已被用于去除异种抗体，而异种灌注技术则用于为异种移植物创造一个合适且熟悉的环境。还尝试了各种分子方法，例如培育表达人类补体调节蛋白（如CD59或衰变加速因子[DAF]）的转基因动物，以下调补体激活，或者通过敲除α-1,3-半乳糖基转移酶基因培育缺乏异种反应性抗原的猪。这些技术与可溶性补体抑制剂（如痘苗病毒补体控制蛋白[VCP]）的联合应用很可能有助于延长移植物存活时间。然而，包括可能出现新的病毒感染在内的各种问题使异种移植这一话题变得复杂。在此讨论介导异种排斥反应干预的不同调节方法和药物。
