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

实验性自身免疫性脑脊髓炎致脑炎T细胞的克隆及免疫机制分析及治疗。

基本信息

批准号：
60480225
负责人：
TABIRA Takeshi
金额：
$ 2.56万
依托单位：
National Center of Neurology and Psychiatry (N C N P) (1986)国立武蔵療養所 (1985)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1986
项目状态：
已结题

项目摘要

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.

1.髓鞘碱性蛋白（MBP）是实验性变态反应性脑脊髓炎（EAE）的致脑炎原。髓鞘蛋白脂质脱辅基蛋白（PLP）是中枢神经髓鞘的主要蛋白成分，20世纪50年代被认为具有致脑炎作用。然而，由于受到MBP污染而被拒绝。本研究证实PLP对豚鼠、大鼠和小鼠均有明确的致脑炎作用。我们还表明，DM-20，PLP的一种成分，诱导慢性复发性EAE与广泛的脱髓鞘在BALB/c小鼠和T细胞系特异性PLP诱导急性和复发性EAE在SJL/J小鼠。这些发现对认识自身免疫性脑脊髓炎尤其是多发性硬化症有重要意义.利用T细胞系和克隆分析EAE的免疫机制建立了MBP特异性致脑炎T细胞系和克隆，并用于分析EAE的细胞机制。我们发现：（1）单个T细胞克隆足以在裸鼠体内诱发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）致脑炎性T细胞克隆可被同种抗原激活并诱发急性EAE.恢复机制及耐受性分析：本实验研究了刘易斯大鼠急性EAE的恢复机制，为开发新的免疫治疗方法提供实验依据。致脑炎性T细胞对持续抗原刺激和环境因素的自限性能力似乎参与了抑制。致脑炎性T细胞克隆的抗血清对EAE的抑制作用正在研究中。