Analysis of pathomechanism of autommune encephalomyelitis and development of new therapeutic strategies.

自身免疫性脑脊髓炎发病机制分析及新治疗策略开发。

• 批准号: 03454245
• 负责人: TABIRA Takeshi
• 金额: $ 4.03万
• 依托单位: National Institute of Neuroscience, NCNP
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454245/
• 关键词: Encephalomyelitis; Multiple Sclerosis; Autommune; T Cell Receptor; Suppressor T; Oligodendroglia; Heat Shock Protein; 熱ショック蛋白; アレルギ-性脳炎; マイクロダイアリシス; ニュ-ロトランスミッタ-

1) Microdialysis of animals with experimental sutoimmune encepha lomyelitis (EAE) did not show difference in serotonin.2) Analysis of T cell receptors of myelin basic protein (MBP) peptide 89-101-specific encephalitogenic T clones revealed diverse V beta usage but certain conserved sequences in the CDR3 region.3) Synthetic peptide of V beta 17a CDR 2 which is utilized by encephalitogenic T cell clones induced double negative suppressors which effectively suppressed EAE in vivo.4) Injection of activated encephalitogenic T cell clones induced antiergotype suppressors. Monoclonal antibodies which recognize the antiergotype antigen were established, and we started cloning of the cDNA.5) We have shown the expression of HSP65 on oligodendrocytes.6) Higher frequency of lymphocytes responding to MBP89-101 or proteolipid protein (PLP) 85-169 was shown in peripheral blood of multiple sclerosis (MS) patients, and immunodominant regions of PLP were speculated. PLP peptide-specific T cell clones utilized diverse B beta s but certain interesting sequences were found in the CDR3 region. These results suggest that new strategies for therapy of EAE can be established by using peptides of T cell receptors and ergotype antigens and this is applicable to human disease MS.

1)对实验性自身免疫性脑脊髓炎（EAE）动物的微透析未显示出神经氨酸的差异。2）对髓鞘碱性蛋白（MBP）肽89-101特异性致脑炎T克隆的T细胞受体的分析显示了不同的V β使用，但在CDR 3区域中存在某些保守序列。致脑炎性T细胞克隆所利用的V β 17 a CDR 2的合成肽诱导了体内有效抑制EAE的双阴性抑制子。4）注射激活的致脑炎T细胞克隆诱导抗麦角型抑制剂。6）多发性硬化（MS）患者外周血淋巴细胞对MBP 89 -101或PLP 85-169的应答频率较高，推测PLP的免疫优势区。PLP肽特异性T细胞克隆利用不同的B β，但在CDR 3区发现了某些感兴趣的序列。这些结果表明，利用T细胞受体肽和麦角型抗原可以建立治疗EAE的新策略，这适用于人类疾病MS。

项目成果

Satoh J et al: "Constitutive expression of 65-kDa heat shock protein (HSP65)- immunoreactivity in cultured mouse oligodendrocytes." Brain Res. 595. 281-290 (1992)

Satoh J 等人：“培养的小鼠少突胶质细胞中 65-kDa 热休克蛋白 (HSP65) 的组成型表达 - 免疫反应性。”

Yamamura T et al: "Analysis of T cell antigen receptors of myelin basic protein specific T cells in SJL/J mice demonstrates an alpha-chain CDR3 motif associated with encephalitogenic T cells." Internat Immunol. (in press). (1994)

Yamamura T 等人：“对 SJL/J 小鼠中髓磷脂碱性蛋白特异性 T 细胞的 T 细胞抗原受体的分析表明，α 链 CDR3 基序与致脑炎 T 细胞相关。”

Yamamura T,Sakanaka S,Takahashi K,Tokuchi F,Kozovska M,Tabira T,: "Homologous T cell receptor complementarity determining region 3 among T cells capable of inducing experimental autoimmune encephalomyelitis." Eur.J.Immunol.

Yamamura T、Sakanaka S、Takahashi K、Tokuchi F、Kozovska M、Tabira T：“T 细胞中同源 T 细胞受体互补决定区 3 能够诱导实验性自身免疫性脑脊髓炎。”

Spurkland A et al: "HLA-DRB1,-DQA1.-DQB1.-DPA1 and -DPB1 genes in Japanese multiple sclerosis patients" Tissue Antigens. 37. 171-173 (1991)

Spurkland A 等人：“日本多发性硬化症患者的 HLA-DRB1、-DQA1.-DQB1.-DPA1 和 -DPB1 基因”组织抗原。

Tabira T et al: "Suppression of lymphocyte spotaneous proliferative response by proteolipid protein peptide in patients with HAM/TSP." Nduroimmunol Res. (in press). (1994)

Tabira T 等人：“蛋白脂质蛋白肽对 HAM/TSP 患者淋巴细胞局部增殖反应的抑制。”