SUPPRESSION OF MULTIPLE SCLEROSIS LIKE DISEASE IN RHESUS MONKEYS

用牛髓鞘碱性蛋白免疫恒河猴 (MBP)和M.结核病H37 RA在弗氏完全佐剂中的表达。 对照组（5/5）发生多发性硬化（MS）样临床 在免疫后20天内出现症状，并在3-5天内安乐死 天后 磁共振成像和尸检 证实了MS病变在大脑和其他区域的存在， 中枢神经系统 试验动物经口给予不同的 剂量的合成共聚物Copaxone（COP-1）显示， 显著减少MS样临床症状。 外周血和脑脊液（CSF）淋巴细胞， 通过流式细胞术分析以确定CD 4 + CD 45 RA + T细胞的变化， 程序性细胞死亡和活化T细胞的存在。 血浆 通过酶联免疫测定法检测样本中MBP特异性 IgG和伊加抗体和T抑制因子。 3 H-胸苷 掺入被用作抗原诱导的淋巴细胞 增殖 对照和试验动物产生显著水平的MBP特异性 IgG和伊加。 对照组的脑脊液淋巴细胞显示， 发病前一周，CD 4 + CD 45 RA-T细胞的数量（>50） 临床症状。 相比之下，来自实验动物的淋巴细胞 与COP-1相比，CD 4 + CD 45 RA + T细胞显著增加， 表明存在T抑制细胞。 分析血浆 在这些研究期间的不同时间收集的数据表明， COP-1处理产生了显著水平的MBP特异性T细胞， 抑制因子 来自对照动物的血浆缺乏MBP特异性T 抑制因子 抗原诱导的增殖研究表明， 对照组和试验组动物的淋巴细胞未显示增殖 当培养物用MBP脉冲时，但这些细胞显示出强烈的 ConA培养的细胞增殖。这些研究与 对H37 RA的纯化蛋白衍生物的强阳性皮肤试验 (PPD)，强烈表明观察到的临床抑制 症状不是由于缺乏IL-2（无反应性）或细胞凋亡。

Rhesus monkeys were immunized with bovine myelin basic protein (MBP) and M. tuberculosis H37RA in Freund's Complete Adjuvant. Controls (5/5) developed multiple sclerosis (MS)-like clinical symptoms within 20 days after immunization and were euthanized 3-5 days later. Magnetic resonance imaging and necropsy examination confirmed the presence of MS lesions in the brain and other regions of the central nervous system. Test animals treated orally with varying doses of the synthetic co-polymer Copaxone (COP-1) showed significantly reduced MS-like clinical symptoms. Peripheral blood and cerebral spinal fluid (CSF) lymphocytes were analyzed by flow cytometry to determine shifts in CD4+CD45RA+ T cells, programmed cell death and the presence of activated T cells. Plasma samples were examined by enzyme-linked immunoassay for MBP-specific IgG and IgA antibodies and T suppressor factors. 3H-thymidine incorporation was used as a measure of antigen-induced lymphocyte proliferation. Control and test animals made significant levels of MBP-specific IgG and IgA. CSF lymphocytes of controls showed an increase in the number (>50) of CD4+CD45RA- T cells one week before the onset of clinical symptoms. In contrast, lymphocytes from test animals treated with COP-1 showed a significant increase in CD4+CD45RA+ T cells, suggesting the presence of T suppressor cells. Analysis of plasma collected at various times during these studies indicate that animals treated with COP-1 produced significant levels of MBP-specific T suppressor factors. Plasma from control animals lacked MBP-specific T suppressor factors. Antigen-induced proliferation studies showed that lymphocytes from control and test animals exhibited no proliferation when cultures were pulsed with MBP, but these cells showed strong proliferation when cultured with Con A. These, studies in consort with strong positive skin tests to a purified protein derivative of H37RA (PPD), strongly suggest that the observed suppression of clinical symptoms is not due to the lack of IL-2 (anergy) or apoptosis.