Jeffrey L, Platt M D
Presse Med. 1992 Dec 2;21(41):1932-8.
Interest in xenotransplantation has dramatically increased in the past 4 years, focusing on the potential use as donors of distantly related animals such as pigs (discordant xenografts). The major barrier is hyperacute rejection. The mechanisms responsible for this rejection include: specific reaction of the recipient's natural antibodies with antigens in the donor's organ, direct activation of the recipient's complement system by endothelial cells in the donor's organ, and/or relative failure of complement inhibitory proteins in the donor's organ to impede activation of the recipient's complement system. In case of vascularized xenograft, the temporary depletion of anti-donor antibodies (anti-ABH or anti-HLA class I) from a graft recipient may allow the long term survival of the graft despite a possible return of the antibodies to the circulation. This phenomenon is called accommodation. The mechanisms involved could be: the endothelial cells in a graft develop a resistance to complement mediated injury; the antigens expressed on the blood vessels become modulated or changed; the natural antibody repertoire changes in such a way that there are fewer anti-donor antibodies. The accommodation phenomenon encourages the view that the barrier to xenotransplantation is not immutable.
在过去4年里,人们对异种移植的兴趣急剧增加,重点关注将关系较远的动物(如猪)作为供体的潜在用途(非协调性异种移植)。主要障碍是超急性排斥反应。导致这种排斥反应的机制包括:受体天然抗体与供体器官中的抗原发生特异性反应、供体器官中的内皮细胞直接激活受体的补体系统,和/或供体器官中补体抑制蛋白相对无法阻止受体补体系统的激活。对于血管化异种移植,移植受体体内抗供体抗体(抗ABH或抗I类HLA)的暂时清除可能使移植器官长期存活,尽管抗体可能会重新回到循环中。这种现象称为适应性改变。其中涉及的机制可能是:移植器官中的内皮细胞对补体介导的损伤产生抗性;血管上表达的抗原被调节或改变;天然抗体库发生变化,使得抗供体抗体减少。适应性改变现象促使人们认为异种移植的障碍并非一成不变。