Histopathology of spleen allograft rejection in miniature swine
Histopathology of spleen allograft rejection in miniature swine
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DOI：
10.1111/j.0959-9673.2005.00414.x
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发表时间：
2005-02-01
影响因子：
3
通讯作者：
Houser, SL
中科院分区：
文献类型：
--
作者：
Dor, FJMF;Gollackner, B;Houser, SL
脾移植（SpTx）已在啮齿动物中建立了供体特异性耐受，但在大型动物或人类中尚未建立。我们报告排斥反应的组织病理学在一个建立的模型SpTx在主要组织相容性复合体（MHC）定义的小型猪。在17个SpTx中，在两个移植物中观察到排斥反应，所述两个移植物移植到未经治疗的、MHC匹配的、次要抗原不同的受体（组1，n = 4）中，但在接受12天疗程的环孢菌素A（CyA）的两个中没有观察到排斥反应。排斥反应也发生在五个移植物移植到完全MHC不同的受体（组2，n = 12），其中一个是未经治疗的，其中四个接受某种形式的免疫抑制治疗。一个接受者的MHC I类不匹配的脾脏治疗12天的CyA没有表现出排斥反应。活检和/或尸检后，用多种染色、免疫组织化学标记和TUNEL测定处理固定的同种异体移植物组织切片。两组移植物发生排斥反应的共同特征，但时间进程不同。第2组和第1组分别在第8天和第27天出现坏死，范围从小动脉壁和窦状隙的局灶性纤维素样坏死到弥漫性坏死，通常伴有出血。排斥反应的其他特征包括非典型细胞引起的白色牙髓扩张以及基底膜和网状纤维染色减少。基线TUNEL指数的加倍发生在组织学可识别的排斥反应之前。本研究建立了诊断的组织学指导方针，也许，在未来的研究中，预测急性排斥反应的脾移植物移植跨越已知的组织相容性障碍，在一个大的动物模型。
Spleen transplantation (SpTx) has established donor-specific tolerance in rodents, but not in large animals or humans. We report the histopathology of rejection in an established model of SpTx in major histocompatibility complex (MHC)-defined miniature swine. Of the 17 SpTx, rejection was observed in two grafts transplanted into untreated, MHC-matched, minor antigen-disparate recipients (group 1, n = 4), but not in the two that received a 12-day course of cyclosporin A (CyA). Rejection also occurred in five grafts transplanted into fully MHC-disparate recipients (group 2, n = 12), one of which was untreated and four of which received some form of immunosuppressive therapy. One recipient of an MHC class-I-mismatched spleen treated with 12 days of CyA did not show rejection. Following biopsy and/or necropsy, fixed allograft tissue sections were treated with multiple stains, immunohistochemical markers and TUNEL assay. Common features of rejection occurred in grafts from both groups, but with varying time courses. Necrosis developed as early as day 8 in group 2 and day 27 in group 1, ranging from focal fibrinoid necrosis of arteriolar walls and sinusoids to diffuse liquefactive necrosis, usually associated with haemorrhage. Other features of rejection included white pulp expansion by atypical cells and decreased staining of basement membranes and reticular fibres. A doubling of the baseline TUNEL index preceded histologically identifiable rejection. This study establishes histologic guidelines for diagnosing and, perhaps, in future studies, predicting acute rejection of splenic allografts transplanted across known histocompatibility barriers in a large-animal model.