Poltorak M, Freed W J
NIMH Neurosciences Center, Saint Elizabeths, Washington, D.C. 20032.
Exp Neurol. 1989 Mar;103(3):222-33. doi: 10.1016/0014-4886(89)90046-0.
The immunological reactions to embryonic cerebellar xenografts (n = 16) and allografts (n = 8) in host rat brain were studied after 2, 4, and 6 weeks of survival and compared to a control group consisting of 10 rats with isografts. Indirect immunofluorescence was performed on fresh frozen brain sections using antibodies against antigen presenting cells (Ia/Ox-6+ cells) and T helper (W3/25+) cells. Massive infiltrations of both cell types were found within xenografts. Ia antigen was present in the walls of small vessels near the transplant as well as in the ventricles on supra- and subependymal cells. In host tissue surrounding the grafts, Ox-6+ immunoreactivity was also observed in a population of cells ranging from an irregular rod-like shape with short branching processes to more rounded cell bodies with retracted processes. The appearance of these cells was characteristic of microglia. These cells were GFAP-negative. These cellular reactions were associated with rejection of the grafts. In contrast, the allografts survived, but nevertheless cells expressing Ox-6+ and to a lesser extent W3/25+ immunoreactivity were found along the injection needle tract and in damaged host tissue surrounding the grafts. No Ox-6+ perivascular infiltrations were seen. Some staining was also found within the allografts, mainly associated with damaged tissue. Ox-6+ ramified cells were also observed. Both Ox-6+ and W3/25+ immunoreactivity decreased with the time of survival. Host and donor GFAP-positive astrocytes did not express Ox-6+ molecules, and therefore probably were not involved in presenting antigen to effector cells. The control isografts also survived very well, but nevertheless Ox-6+ and less widespread W3/25+ cells were present in surrounding injured host tissue. Ox-6+ perivascular infiltration was not found in the host brain of animals with isografts. Ox-6+ and W3/25+ immunoreactivities were present primarily in graft areas that appeared damaged, often closely associated with injured host tissue. These results indicate that the process of implantation of grafts and associated brain injury induces enhanced Ia/Ox-6+ immunoreactivity, primarily on microglia in brain parenchyma surrounding grafts, and suggest that host microglia may substantially contribute to the initiation of immune reactions against intracerebral grafts. Despite this predisposition to an immunological response, only in the case of xenografts did these reactions, with the addition of Ox-6+ perivascular cuffing and cell infiltrations within the grafts, lead ultimately to graft rejection.
研究了宿主大鼠脑内胚胎小脑异种移植物（n = 16）和同种移植物（n = 8）在存活2周、4周和6周后的免疫反应，并与由10只接受同基因移植物的大鼠组成的对照组进行比较。使用针对抗原呈递细胞（Ia/Ox-6+细胞）和辅助性T细胞（W3/25+细胞）的抗体，对新鲜冷冻的脑切片进行间接免疫荧光检测。在异种移植物内发现了这两种细胞类型的大量浸润。Ia抗原存在于移植物附近小血管壁以及脑室的室上和室管膜下细胞中。在移植物周围的宿主组织中，在一群细胞中也观察到了Ox-6+免疫反应性，这些细胞从具有短分支突起的不规则棒状形态到具有收缩突起的更圆形细胞体不等。这些细胞的外观是小胶质细胞的特征。这些细胞GFAP呈阴性。这些细胞反应与移植物的排斥有关。相比之下，同种移植物存活了下来，但在注射针道沿线以及移植物周围受损的宿主组织中，仍发现了表达Ox-6+以及程度较轻的W3/25+免疫反应性的细胞。未观察到Ox-6+血管周围浸润。在同种移植物内也发现了一些染色，主要与受损组织有关。还观察到了Ox-6+分支状细胞。随着存活时间的延长，Ox-6+和W3/25+免疫反应性均降低。宿主和供体GFAP阳性星形胶质细胞不表达Ox-6+分子，因此可能不参与向效应细胞呈递抗原。对照组的同基因移植物也存活得很好，但在周围受损的宿主组织中仍存在Ox-6+以及分布较少的W3/25+细胞。在接受同基因移植物的动物的宿主脑中未发现Ox-6+血管周围浸润。Ox-6+和W3/25+免疫反应性主要存在于出现损伤的移植物区域，通常与受损的宿主组织密切相关。这些结果表明，移植物植入过程及相关的脑损伤会诱导Ia/Ox-6+免疫反应性增强，主要在移植物周围脑实质的小胶质细胞上，并表明宿主小胶质细胞可能在针对脑内移植物的免疫反应启动中起重要作用。尽管有这种免疫反应的倾向，但只有在异种移植物的情况下，这些反应加上Ox-6+血管周围套袖形成和移植物内的细胞浸润，最终导致移植物排斥。
