猕猴预致敏后肾移植加速性排斥反应的免疫学及病理学特点

Immunologic and pathologic features of an accelerated rejection model of renal allotransplantation in rhesus monkeys

目的观察猕猴预致敏后肾移植加速性排斥反应的免疫学及病理学变化特点。方法建立猕猴皮肤预致敏后肾移植加速性排斥反应模型（供、受者各3只）。检测3只受者皮肤移植预致敏前、后及肾移植后血清内供者特异性抗体的变化，并在发生排斥反应时对移植肾进行免疫组织化学（测定补体、抗体的沉积及各类型淋巴细胞浸润情况）及病理学分析。结果3只受者均发生了加速性排斥反应。其中2只受者在预致敏后血清中供者特异性抗体明显增加，对供者的淋巴毒反应明显升高；肾移植后受者血清中供者特异性抗体及针对供者的淋巴毒进一步升高。苏木精－伊红染色显示排斥反应的移植肾内有明显的动脉坏死、血栓形成、间质出血、中性粒细胞浸润；免疫组织化学及荧光染色显示移植肾内有大量的补体、抗体沉积（主要为IgG），而各种类型的淋巴细胞浸润少见。另1只受者体内的供者特异性抗体及对供者淋巴毒反应的升高程度不如前2只明显，病理学变化以肾小管损伤为主。结论皮肤移植预致敏可以诱导受者产生程度不等的预存抗体，导致大多数移植肾在术后早期发生主要由抗体和补体介导的严重的急性体液性排斥反应。

Objective To study the immunologic and pathologic features of an accelerated rejection model of renal altotransplantation in presensitized monkeys. Methods The accelerated rejection model of renal allotransplantation was established in presensitized monkeys, which received donor skin transplantation in advance （n = 3）. The changes of donor specific antibody （DSA） levels in the recipient monkeys before/after skin and kidney transplantation were measured. The kidney grafts were examined for routine pathology, antibody and complement depositions, various lymphocyte subsets infiltration by HE staining, immunofluorescence, or immunohistochemistry. Results All renal allografts in 3 presensitized monkeys developed accelerated rejection within 4 days. In 2 presentized monkeys, the levels of DSA and their mediated complement-dependent cytotoxicity （CDC） were significantly increased after skin transplantation, and further markedly elevated at the time of kidney graft rejection. In the rejected renal grafts, massive （23, CA, C5b-9 and IgG deposits with few lymphocytes infiltration were found. Typical pathologic changes included severe arterionecrosis, thrombosis, interstitial hemorrhage, and infiltration of neutrophils. In the rest one presentized monkey, the levels of DSA and CDC were only marginally increased, and the pathological changes of the rejected renal graft were characterized mainly by the injury of renal tubules. Conclusion Presensitization by donor skin transplantation could elevate the levels of DSA and CDC in recipient monkeys, which resulted in severe antibody-mediated acute humoral rejection in most of the following renal transplants.