Matsumoto Y, Fujiwara M
J Neurol Sci. 1987 Jan;77(1):35-47. doi: 10.1016/0022-510x(87)90204-8.
In order to examine developing lesions of experimental allergic encephalomyelitis (EAE) at the preclinical stage, adoptive transfer of EAE was achieved in Lewis rats using spleen cells obtained from rats previously immunized with 50 micrograms of guinea pig myelin basic protein (MBP) in complete Freund's adjuvant. After cell transfer, all the recipient rats developed severe paraparesis with minimal variation in the onset of clinical signs, which facilitated immunohistochemical examination of developing lesions of EAE in asymptomatic animals. The initial pathological finding detected in this system was an increased number of inflammatory cells (both OX19+ and OX8+ T cells and macrophages) in the subarachnoid space (SAS) which was observed on day 3 post-transfer (PT) when the recipient animals showed no neurological abnormalities. By day 4 PT, inflammatory cells were detected in the Virchow-Robin space of vessels which were continuous to the SAS. Perivascular lymphocytic infiltration was scarcely detected in the gray matter. On day 5 PT, the rats showed severe paraparesis. Inflammatory foci increased in number and were detected in both the white and gray matter. Diffuse parenchymal T-lymphocyte infiltration was also recognized at this stage. From day 6 PT onwards, inflammatory cells decreased gradually. On day 8 PT, all the rats recovered from EAE and few inflammatory cells were detected in the parenchyma and SAS. Immunohistochemical examination of T-cell subsets and Ia antigens revealed that the number of OX19+ cells was greater than that of OX8+ cells in the parenchyma and SAS at all stages examined, the distribution of OX19+ cells was almost the same as that of OX8+ cells, OX8+ cells decreased in number before clinical signs subsided, and that after the infiltration of T cells into the parenchyma, cells with dendritic morphology (microglia) expressed Ia antigens in close association with the infiltrating T cells. Adoptive transfer of MBP-sensitized spleen cells provides constant induction of EAE with minimal variation in clinical onset and severity, thus being a useful model for the examination of early events of EAE.
为了在临床前阶段检查实验性变应性脑脊髓炎（EAE）的发展性病变，采用先前用50微克豚鼠髓鞘碱性蛋白（MBP）在完全弗氏佐剂中免疫的大鼠的脾细胞，在Lewis大鼠中实现EAE的过继转移。细胞转移后，所有受体大鼠均出现严重的双下肢轻瘫，临床症状出现时间的变化极小，这便于对无症状动物中EAE的发展性病变进行免疫组织化学检查。在该系统中检测到的最初病理发现是蛛网膜下腔（SAS）中炎性细胞（OX19 +和OX8 + T细胞以及巨噬细胞）数量增加，在转移后第3天（PT）观察到，此时受体动物未表现出神经学异常。到PT第4天，在与SAS相连的血管的Virchow-Robin间隙中检测到炎性细胞。在灰质中几乎未检测到血管周围淋巴细胞浸润。PT第5天，大鼠出现严重的双下肢轻瘫。炎性病灶数量增加，在白质和灰质中均检测到。在此阶段也识别出弥漫性实质T淋巴细胞浸润。从PT第6天起，炎性细胞逐渐减少。PT第8天，所有大鼠从EAE中恢复，在实质和SAS中检测到的炎性细胞很少。T细胞亚群和Ia抗原的免疫组织化学检查显示，在所有检查阶段，实质和SAS中OX19 +细胞的数量均多于OX8 +细胞，OX19 +细胞的分布与OX8 +细胞几乎相同，OX8 +细胞在临床症状消退前数量减少，并且在T细胞浸润到实质后，具有树突形态的细胞（小胶质细胞）与浸润的T细胞紧密相关地表达Ia抗原。MBP致敏脾细胞的过继转移可持续诱导EAE，临床发病和严重程度的变化极小，因此是检查EAE早期事件的有用模型。
