Time-dependent expression of donor- and host-specific major histocompatibility complex class I and II antigens in allogeneic dopamine-rich macro- and micrografts:: comparison of two different grafting protocols
Time-dependent expression of donor- and host-specific major histocompatibility complex class I and II antigens in allogeneic dopamine-rich macro- and micrografts:: comparison of two different grafting protocols
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DOI：
10.1007/s004010050769
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发表时间：
1998-01-01
影响因子：
12.7
通讯作者：
Nikkhah, G
中科院分区：
文献类型：
--
作者：
Brandis, A;Kuder, H;Nikkhah, G
神经移植作为帕金森病的一种治疗方法，仍然需要同种异体移植材料，并提出了免疫抑制和移植排斥的问题。本研究调查了主要组织相容性复合物（MHC）表达和星形胶质细胞反应的时间过程中异基因多巴胺能移植物，比较两种不同的移植方案。成年6-羟基多巴胺损伤的刘易斯1.W大鼠接受来自DA大鼠胎儿腹侧中脑的纹状体内细胞悬液移植物，通过金属套管作为单个l-pl巨移植物或通过玻璃毛细管作为四个250 nl/存款的微移植物。未给予免疫抑制剂。移植后1，3，6和12周进行免疫组化，使用抗体对供体和宿主特异性MHC I类和II类抗原，胶质细胞酸性蛋白（GFAP）和酪氨酸羟化酶（TH）。大多数动物在移植后12周内表现出良好的同种异体移植物存活，没有排斥反应的迹象。TH阳性神经突起的损伤纹状体的神经再支配观察从3-6 wk on. Expression的供体特异性MHC I类在两个同种异体移植组中均较低，而宿主MHC I类和II类反应以及星形胶质细胞反应倾向于较高的macrografted动物。在任何时间点均未观察到供体MHC II类。可以得出结论，胎儿中脑细胞悬液的实质内同种异体移植物可以在大鼠帕金森模型中存活至少12周，而无需免疫抑制，并且适量的供体特异性MHC I类抗原的表达不足以启动排斥反应过程。此外，微移植方法可以降低创伤水平和随后的MHC和GEAR表达，从而可以最大限度地减少移植物排斥反应的风险。
Neural transplantation, as a therapeutic approach to Parkinson's disease, still requires allogeneic graft material and raises questions of immunosuppression and graft rejection. The present study investigated the time course of major histocompatibility complex (MHC) expression and astrocytic response in allogeneic dopaminergic grafts, comparing two different grafting protocols. Adult 6-hydroxydopamine-lesioned Lewis 1.W rats received intrastriatal cell suspension grafts from the ventral mesencephalon of DA rat fetuses, either as single l-pl macrograft via metal cannula or as four micrografts of 250 nl/deposit via a glass capillary. No immunosuppression was administered. Immunohistochemistry was performed at 1, 3, 6, and 12 weeks after grafting, using antibodies against donor-and host-specific MHC class I and II antigen, glial fibrillary acidic protein (GFAP) and tyrosine hydroxylase (TH). Most animals showed good allograft survival up to 12 weeks after transplantation with no signs of rejection. Reinnervation of the lesioned striatum by TH-positive neurites was observed from 3-6 weeks on. Expression of donor-specific MHC class I was comparably low in both allogeneic grafting groups, while host MHC class I and II reaction as well as astrocytic response tended to be higher in the macrografted animals. Donor MHC class II was not observed at any time point. It is concluded that intraparenchymal allografts of fetal mesencephalic cell suspensions can survive well in the rat Parkinson model without immunosuppression for at least 12 weeks, and that the expression of moderate amounts of donor-specific MHC class I antigen does not suffice to initiate a rejection process. In addition, the microtransplantation approach may reduce the level of trauma and subsequent MHC and GEAR expression and may, thereby, minimize the risk of graft rejection.