Sobel R A, Blanchette B W, Russo M A, Williams A M, Colvin R B
J Immunol. 1987 Apr 15;138(8):2507-13.
To determine the effects of anti-T cell monoclonal antibody-induced systemic T cell depletion in neuro-autoimmune disease, we studied the in vivo effects of 8BE6, a mouse anti-guinea pig (GP) pan-T cell monoclonal antibody, on the course and immunopathology of the disease model experimental allergic encephalomyelitis (EAE) in adult Strain 13 GP. Central nervous system (CNS) tissues were studied by routine histology and by an immunoperoxidase staining technique using monoclonal antibodies to T cells, IgM, and macrophages. From 3 days before to 10 days after sensitization with GP spinal cord and complete Freund's adjuvant, the GP were given one or two i.p. doses of 3.4 mg 8BE6 or MOPC 21, the parent mouse myeloma ascites, or normal saline. Eighteen of 18 control-treated GP developed typical acute, paralytic EAE 11 to 21 days after sensitization, whereas acute EAE was prevented in 33 of 49 8BE6-treated GP (67%), and the onset was delayed and disease progression was slowed in the others. Five GP treated with 8BE6 from days 11 to 14 after sensitization, at the onset of neurologic signs, rapidly deteriorated within hours after treatment and had loss of T cell staining, and lymphocytolysis in the CNS. 8BE6-treated GP which did not develop acute EAE were observed daily for up to 700 days (mean = 213 days). Twenty-nine of 39 (74%) had from one to six relapses or fixed neurologic deficits. GP in relapse were additionally treated with 8BE6 (22), MOPC-21 (5), or saline (6) in a cross-over protocol. Clinical scores were improved from days 2 to 12 after treatment (p less than 0.05), and complete recovery within 30 days occurred more frequently (p = 0.046) and more rapidly (p less than 0.01), after 8BE6 as compared with control treatments. Recoveries occurred more often if 8BE6 was given early in the relapse. Multiple treatments led to dose-dependent levels of serum antibodies to mouse immunoglobulin detected by an ELISA. There were no differences between acute and chronic EAE in numbers of inflammatory foci or numbers of macrophages and T cells in CNS infiltrates, but GP with chronic EAE had more extensive demyelination and vascular fibrosis and more numerous IgM+ B cells in parenchymal and meningeal infiltrates than in acute EAE (p less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)
为了确定抗T细胞单克隆抗体诱导的全身T细胞耗竭在神经自身免疫性疾病中的作用，我们研究了小鼠抗豚鼠（GP）全T细胞单克隆抗体8BE6对成年13号品系GP实验性变态反应性脑脊髓炎（EAE）疾病模型病程及免疫病理学的体内影响。通过常规组织学以及使用针对T细胞、IgM和巨噬细胞的单克隆抗体的免疫过氧化物酶染色技术对中枢神经系统（CNS）组织进行研究。在用GP脊髓和完全弗氏佐剂致敏前3天至致敏后10天，给GP腹腔注射1或2剂3.4 mg的8BE6或其亲本小鼠骨髓瘤腹水MOPC 21，或生理盐水。18只接受对照处理的GP中有18只在致敏后11至21天出现典型的急性麻痹性EAE，而49只接受8BE6处理的GP中有33只（67%）预防了急性EAE，其他GP发病延迟且疾病进展减缓。在致敏后第11至14天出现神经症状时用8BE6处理的5只GP在治疗后数小时内迅速恶化，CNS中T细胞染色缺失且出现淋巴细胞溶解。对未发生急性EAE的8BE6处理的GP每天观察长达700天（平均 = 213天）。39只中有29只（74%）有1至6次复发或固定的神经功能缺损。复发的GP在交叉方案中额外接受8BE6（22只）、MOPC - 21（5只）或生理盐水（6只）治疗。治疗后第2至12天临床评分改善（p < 0.05），与对照治疗相比，8BE6治疗后30天内完全恢复更频繁（p = 0.046）且更迅速（p < 0.01）。如果在复发早期给予8BE6，恢复更常见。多次治疗导致通过ELISA检测到的抗小鼠免疫球蛋白血清抗体水平呈剂量依赖性。急性和慢性EAE在CNS浸润中的炎症灶数量、巨噬细胞和T细胞数量方面无差异，但与急性EAE相比，慢性EAE的GP有更广泛的脱髓鞘和血管纤维化，实质和脑膜浸润中有更多的IgM + B细胞（p < 0.001）。（摘要截断于400字）
