Schluesener H J, Sobel R A, Weiner H L
Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115.
J Neuroimmunol. 1988 Jul;18(4):341-51. doi: 10.1016/0165-5728(88)90055-0.
We used a new version of experimental autoimmune encephalomyelitis (EAE) in the rat to investigate immunotherapy of demyelination during autoimmune disease of the central nervous system (CNS). Encephalitis was induced by immunization of rats with myelin basic protein (MBP), and demyelination by systemic injection of a monoclonal antibody, 8-18C5, specific for a myelin/oligodendrocyte glycoprotein (MOG). Antibody injection resulted in hyperacute disease progression and extensive demyelination throughout the CNS. Immunotherapy of antibody-induced demyelination was possible with another monoclonal antibody, pta-3, specific for activated rat T cells. These findings demonstrate the synergy of T cell-mediated and antibody-dependent processes in rat CNS demyelination in vivo. Histologically, immunotherapy reduced the numbers of meningeal mononuclear cell inflammatory foci, but not parenchymal inflammation in the early phase of demyelinating disease. Animals which had received pta-3 antibody had less inflammation than untreated rats in the convalescent phase. Multiple pta-3 treatments most effectively suppressed inflammation. Furthermore, antibody-treated rats with demyelination developed a series of neurologic signs, including pronounced spasticity; that were not observed in control EAE rats and thus appears to be associated with the demyelinating process.
我们在大鼠中使用了一种新型实验性自身免疫性脑脊髓炎（EAE）来研究中枢神经系统（CNS）自身免疫性疾病期间脱髓鞘的免疫治疗。通过用髓鞘碱性蛋白（MBP）免疫大鼠诱导脑炎，通过全身注射针对髓鞘/少突胶质细胞糖蛋白（MOG）的单克隆抗体8-18C5诱导脱髓鞘。抗体注射导致超急性疾病进展和整个CNS广泛脱髓鞘。用另一种针对活化大鼠T细胞的单克隆抗体pta-3对抗体诱导的脱髓鞘进行免疫治疗是可行的。这些发现证明了T细胞介导的过程和抗体依赖性过程在大鼠CNS体内脱髓鞘中的协同作用。组织学上，免疫治疗减少了脱髓鞘疾病早期脑膜单核细胞炎性病灶的数量，但未减少实质炎症。接受pta-3抗体的动物在恢复期的炎症比未治疗的大鼠少。多次pta-3治疗最有效地抑制了炎症。此外，经抗体治疗的脱髓鞘大鼠出现了一系列神经体征，包括明显的痉挛；在对照EAE大鼠中未观察到这些体征，因此似乎与脱髓鞘过程有关。
