猪到猕猴异种心脏移植超急性排斥反应的免疫学及病理学变化

目的观察猪到猕猴异种心脏移植超急性排斥反应时的免疫学及病理学变化。方法采用猪到猕猴腹腔内异位心脏移植模型,检测发生超急性排斥反应者的血液中补体、天然抗体及T淋巴细胞亚群的变化,并对移植心脏进行免疫组化(测定C3、C4、C5b9、IgG及IgM的沉积)及病理学分析。结果发生超急性排斥反应时,血清补体C3、C4的含量、总补体活性及抗猪内皮细胞天然抗体均有一定程度的下降;CD4 /CD8 T淋巴细胞的比率也有所下降;移植心脏中均有补体C3、C4、C5b9的沉积,IgG及IgM也均有沉积,但IgG和IgM沉积强度的差异无统计学意义;病理学改变主要为心肌间质弥漫性出血、水肿,毛细血管内普遍淤血。结论补体通过经典途径激活参与猪到猕猴异种心脏移植超急性排斥反应;超急性排斥反应时受者血中天然抗体水平明显下降;CD4 T淋巴细胞可能参与异种移植超急性排斥反应过程并有所消耗;发生超急性排斥反应的移植物突出病理表现为间质出血。

Immunologic and pathologic features of hyperacute rejection after pig-to-primate heart xenotransplantation

Objective To study the immunologic and pathologic features of hyperacute rejection after pig-to-primate heart xenotransplantation. Methods By using the model of pig-to-primate ~abdominal heart xenotransplantation, the changes of blood complement activity, natural antibody and T lymphocytic subsets in the patients with hyperacute rejection were measured. The cardiac xenografts were examined for C3, C4, C5b-9, deposit of IgG and IgM by immunohistochemistry and pathological ~analysis . Results The C3, C4 levels, complement activity and anti-pig endotheliocyte xenoantibody were decreased to some extent in the serum after hyperacute rejection, and the ratio of CD4 /CD8 T cell was also decreased. In the cardiac xenografts, three were C3, C4, C5b-9, IgG and IgM deposits to ~varying degrees, but there was no significant difference in the deposits of IgG and IgM. ~Pathological changes included hemorrhage and edema throughout the myocardium, with capillary ~congestion , but no gross intravascular thrombosis or cellular infiltration was seen. Conclusion (1) HAR in this discordant xenograft model of pig-to-monkey was caused by primary activation of complement via the classic pathway. (2) The natural antibody was obviously decreased during HAR. (3) CD4 -T cell may be involved in the HAR. (4) Interstitial hemorrhage was the most marked histopathologic feature of the HAR in this discordant xenograft model.