Addition of allogeneic spleen cells causes rejection of intrastriatal embryonic mesencephalic allografts in the rat
Addition of allogeneic spleen cells causes rejection of intrastriatal embryonic mesencephalic allografts in the rat
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DOI：
10.1016/s0306-4522(96)00470-8
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发表时间：
1997-03-01
期刊：
影响因子：
3.3
通讯作者：
Widner, H
中科院分区：
文献类型：
--
作者：
Duan, WM;Brundin, P;Widner, H
为了说明抗原提呈细胞对脑内同种异体神经移植物存活的重要性，在移植前将同种异体脾细胞添加到移植物组织中。从近交系刘易斯或Sprague-Dawley大鼠制备分离的胚胎、富含多巴胺的中脑和成年脾组织。将神经细胞和脾细胞的混合物立体定向移植到成年Sprague-Dawley大鼠的右侧纹状体中。对照组为不添加同种异体脾细胞的同种异体神经移植物和添加或不添加同系脾细胞的同系神经移植物。移植后6周，对脑切片进行酪氨酸羟化酶免疫细胞化学处理，特异性移植多巴胺神经元，以及免疫和炎症反应中各种成分的标记物库。同种异体神经移植物与同种异体脾细胞混合后出现排斥反应。在这些大鼠中，有高水平的主要组织相容性复合物I类和II类抗原的表达，强烈的细胞浸润，包括巨噬细胞和活化的小胶质细胞，并存在分化4-和8-免疫反应性细胞簇的移植部位。此外，在发生排斥反应的移植物内和周围，细胞间粘附分子-1、肿瘤坏死因子-α和白细胞介素-6水平升高。与此相反，同系神经移植物存活良好，无论它们是否与同系脾细胞混合，对照神经同种异体移植物也表现出未受损的存活。后三组移植多巴胺神经元的数量无显著差异。炎症和排斥反应的不同标志物的表达水平在这些移植物中一般低于植入物的组合同种异体神经和脾cells.In总结，纹状体内的神经同种异体移植物，通常存活良好，在我们的动物模型，被拒绝，如果同种异体脾细胞从同一供体被添加到移植组织。添加的脾细胞引起强烈的宿主免疫和炎症反应。这项研究支持了这样一种观点，即大脑的免疫豁免并不能对免疫组织不相容的神经移植物提供绝对的保护。(C)1997年IBRO。
To address the importance of antigen-presenting cells for the survival of intracerebral neural allografts, allogeneic spleen cells were added to the graft tissue before transplantation. Dissociated embryonic, dopamine-rich mesencephalic and adult spleen tissues were prepared from either inbred Lewis or Sprague-Dawley rats. A mixture of neural and spleen cells was stereotaxically transplanted into the right striatum of adult Sprague-Dawley rats. Controls were neural allografts without addition of allogeneic spleen cells and syngeneic neural grafts with or without the addition of syngeneic spleen cells. Six weeks after transplantation, brain sections were processed immunocytochemically for tyrosine hydroxylase, specific for grafted dopamine neurons, and a bank of markers for various components in the immune and inflammatory responses. The neural allografts which were mixed with allogeneic spleen cells were rejected. In these rats, there were high levels of expression of major histocompatibility complex class I and II antigens, intense cellular infiltration including macrophages and activated microglial cells, and a presence of cluster of differentiation 4- and 8-immunoreactive cells in the graft sites. Moreover, there were increased levels of intercellular adhesion molecule-1, tumour necrosis factor-alpha and interleukin-6 in and around the grafts which were undergoing rejection. In contrast, syngeneic neural grafts survived well regardless of whether they were mixed with syngeneic spleen cells or not, and control neural allografts also exhibited unimpaired survival. No significant difference was observed in the number of grafted dopamine neurons among these three latter groups. The levels of expression of the different markers for inflammation and rejection were generally lower in these grafts than in implants of combined allogeneic neural and spleen cells.In summary, intrastriatal neural allografts, which normally survive well in our animal model, were rejected if allogeneic spleen cells from the same donor were added to the graft tissue. The added spleen cells caused strong host immune and inflammatory responses. The study gave support to the notion that immunological privilege of the brain does not provide absolute protection to immunogenetically histoincompatible neural grafts. (C) 1997 IBRO.