Duan W M, Cameron R M, Brundin P, Widner H
Wallenberg Neuroscience Center, Department of Physiology and Neuroscience, Lund University Sölvegatan 17, Sweden.
Exp Neurol. 1997 Nov;148(1):334-47. doi: 10.1006/exnr.1997.6656.
The present study was designed to address two questions. First, can an intrastriatal neural allograft exhibit long-term survival (18 weeks) if the host is immunized by an orthotopic skin graft 6 weeks after neural transplantation (the 6w-Long group)? Second, can an intrastriatal neural allograft survive when the host is challenged by an orthotopic skin allograft either simultaneously (Sim) with the intracerebral graft surgery or 2 (2w) weeks later? Dissociated embryonic ventral mesencephalic tissue from Lewis rats was stereotaxically injected into the striatum of Sprague-Dawley rats with unilateral 6-hydroxydopamine lesions. Six weeks after neural grafting, no reduction in amphetamine-induced motor asymmetry was observed in the Sim and 2w groups. At 6 weeks after skin grafting, the mean motor asymmetry scores had returned to the initial pretransplantation levels in the 6w-Long group. All the neural allografts in the Sim group were completely rejected, and the mean number of tyrosine hydroxylase immunoreactivity neurons in the grafts was significantly reduced in the 2w and the 6w-Long group, when compared to the no-skin control group. There were very high levels of expression of MHC class I and II antigens, marked cellular infiltrates containing macrophages and T-lymphocytes, and several activated microglia and astrocytes in and around the surviving intracerebral transplants in the 2w and the 6w-Long groups. The results suggest that intrastriatal neural allografts are more likely to be rejected rapidly if the host is efficiently immunized with the same alloantigens simultaneously or soon after the neural transplantation than at a later time point. When established neural allografts are subjected to a strong immunological challenge, they undergo protracted rejection.
本研究旨在解决两个问题。第一，如果在神经移植后6周（6周长期组）用原位皮肤移植对宿主进行免疫，纹状体内神经同种异体移植能否长期存活（18周）？第二，当宿主在脑内移植手术同时（Sim组）或2周（2周组）后受到原位皮肤同种异体移植的攻击时，纹状体内神经同种异体移植能否存活？将来自Lewis大鼠的解离胚胎腹侧中脑组织立体定向注射到单侧6-羟基多巴胺损伤的Sprague-Dawley大鼠的纹状体中。神经移植6周后，Sim组和2周组未观察到苯丙胺诱导的运动不对称性降低。皮肤移植6周后，6周长期组的平均运动不对称性评分已恢复到移植前的初始水平。Sim组的所有神经同种异体移植均被完全排斥，与无皮肤对照组相比，2周组和6周长期组移植中酪氨酸羟化酶免疫反应性神经元的平均数量显著减少。在2周组和6周长期组存活的脑内移植及其周围，MHC I类和II类抗原表达水平非常高，有含有巨噬细胞和T淋巴细胞的明显细胞浸润，以及一些活化的小胶质细胞和星形胶质细胞。结果表明，如果宿主在神经移植同时或之后不久用相同的同种异体抗原进行有效免疫，纹状体内神经同种异体移植比在稍后时间点更有可能迅速被排斥。当已建立的神经同种异体移植受到强烈的免疫攻击时，它们会经历长期排斥。
