Cloning of encephalitogenic T cells and analysis of immune mechanisms and treatment of experimental autoimmune encephalomyelitis.

1. 发现一种新的脑致病菌。髓鞘碱性蛋白（myelin basic protein， MBP）是实验性变应性脑脊髓炎（EAE）的脑原。髓磷脂载脂蛋白（PLP）是中枢神经髓磷脂的主要蛋白质成分，在20世纪50年代被认为具有致脑性。然而，由于被MBP污染，它被拒绝了。本研究在豚鼠、大鼠和小鼠中证实了PLP是一种明确的脑原。我们还发现，PLP的一种成分DM-20在BALB/c小鼠中诱导慢性复发性EAE并伴有广泛的脱髓鞘，PLP特异性T细胞系在SJL/J小鼠中诱导急性和复发性EAE。这些发现有助于认识自身免疫性脑脊髓炎，特别是多发性硬化症。利用T细胞系和克隆分析EAE的免疫机制。建立了mbp特异性致脑T细胞系和克隆，用于分析EAE的细胞机制。我们发现：(1)单个T细胞克隆足以在裸鼠中诱导全面的EAE， (2) Ia抗原在急性期和复发期的中枢神经系统病变中表达，(3)一个致脑性T细胞克隆可以被异体抗原激活并诱导急性EAE。恢复机理及耐受性分析。为了开发新的免疫治疗方法，我们对Lewis大鼠急性EAE的恢复机制进行了研究。脑源性T细胞对持续抗原刺激和环境因素的自我限制能力似乎参与了抑制。用抗血清抑制EAE对致脑性T细胞克隆的作用目前正在研究中。

1. Finding of a novel encephalitogen.It is well known that myelin basic protein (MBP) is an encephalitogen of experimental allergic encephalomyelitis (EAE). Myelin proteolipid apoprotein (PLP), a major protein component of central nerve myelin, was thought to be encephalitogenic in 1950s. However, it was denied because of contamination with MBP. This study has proven that PLP is a definite encephalitogen in guinea pigs, rats and mice. We have also shown that DM-20, a component of PLP, induces chronic relapsing EAE with widespread demyelination in BALB/c mice and T cell lines specific for PLP induce acute and relapsing EAE in SJL/J mice. These findings significantly contributed to the understanding of autoimmune encephalomyelitis especially of multiple sclerosis.2. Analysis of immune mechanisms of EAE using T cell lines and clones.MBP-spepcific encephalitogenic T cell lines and clones were established and used for analysis of cellular mechanism of EAE. We found that (1) a single T cell clone is enough to induce full-blown EAE in nude mice, (2) Ia antigens are expressed in the central nervous system lesions at acute and relapsed stage, and (3) an encephalitogenic T cell clone can be activated by allo-antigens and induces acute EAE.3. Analysis of recovery mechanism and tolerance.In order to develope new immunological treatment, we have studied recovery mechanism of acute EAE in Lewis rats. Self-limited ability of encephalitogenic T cells to continuous antigenic stimulation and environmental factors seem to be involved in the suppression. Suppression of EAE with antiserum to encephalitogenic T cell clone is now under study.