Failure to induce experimental allergic encephalitis in mice lucking expression of SLC chemokine.

未能在幸运表达 SLC 趋化因子的小鼠中诱发实验性过敏性脑炎。

• 批准号: 12670621
• 负责人: KAKIUCHI Terutaka
• 金额: $ 2.24万
• 依托单位: Toho University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670621/
• 关键词: plt mouse; SLC chemokine; ELC chemokine; experimental allergic encephalitis; T cell; regulation of T cell response; multiple sclerosis; 実験的アレルギー性脳脊髄炎

Experimental allergic encephalitis (EAE) is a mouse model of human multiplesclerosis. Paucity of lymph node T cells (plt) mouse lacks expression of SLC (CCL21) and ELC (CCL19) chemokines. Immunization with MOG peptide induces experimental allergic encephalitis in control mice, but not in plt mice. When T cells were transferred from +/plt-C56BL/6mice immunized with MOG peptide into pltmice, EAE was deloped, suggesting that failure to develop EAE in pltmice was not due to migration failure induced by lacking chemokine expression, but due to effector T cell developmentpltmice lack expression of SLC and ELC chemokines, but T cell response to subcutaneous immunization with a protein antigen was rather higher than in control mice and prolonged much longer than in control mice. These findings suggest that T cell immune regulation is insufficient in pltmice. Apoptosis in draining lymph mode in pltmice was much less evident in pltmice than in control mice, which resulted in keeping increased number of responding T cells. To elucidate the mechanisms for the failure to develop EAE in pltmice, we will analyze effector CD4+ T cells after immunization with protein antigen

实验性变态反应性脑炎(EAE)是人类多发性硬化症的小鼠模型。缺乏淋巴节T细胞(PLT)的小鼠缺乏SLC(CCL21)和ELC(CCL19)趋化因子的表达。MOG多肽免疫可诱导对照组小鼠实验性变态反应性脑炎，但对PLT小鼠无明显影响。将MOG多肽免疫的+/PLT-C56BL/6小鼠的T细胞转移到plt小鼠体内后，出现了EAE，提示plt小鼠未能发生EAE不是由于缺乏趋化因子表达所致的迁移失败，而是由于效应性T细胞发育缺乏SLC和ELC趋化因子的表达，而对蛋白抗原皮下免疫的T细胞应答明显高于对照小鼠，且持续时间比对照小鼠长得多。这些发现表明，PLT小鼠T细胞免疫调节不足。PLT小鼠在引流淋巴模式下的细胞凋亡明显低于对照组，这导致应答T细胞的数量持续增加。为了阐明PLT小鼠未能发生EAE的机制，我们将分析蛋白质抗原免疫后的效应者CD4+T细胞

项目成果

M Terabe, M Shimizu, A Mabuchi, S Matui, H Morikawa, K Kaneda, T Kakiuchi, K Yokomuro: "Unresponsiveness of intrahepatic lymphocytes to bacterial superantigen rapid development of suppressive Mac-1 cells in the mouse liver"Hepatology. 32. 507-513 (2001)

M Terabe、M Shimizu、A Mabuchi、S Matui、H Morikawa、K Kaneda、T Kakiuchi、K Yokomuro：“肝内淋巴细胞对小鼠肝脏中抑制性 Mac-1 细胞的细菌超抗原快速发展无反应”肝病学。

Y Iwasaki, Y Ichikawa, O Igarashi, M Kinoshita, K Ikeda: "Tropic effect of olmesartan, a novel AT1R antagonist, on spinal motor neurons in vitro and in vivo"Neurol.Res.. 24. 468-472 (2002)

Y Iwasaki、Y Ichikawa、O Igarashi、M Kinoshita、K Ikeda：“奥美沙坦（一种新型 AT1R 拮抗剂）对脊髓运动神经元的体外和体内作用”Neurol.Res.. 24. 468-472 (2002)

F Ishikawa, H Nakano, A Seo, Y Okada, H Torihata, Y Tanak, T Uchida, H Miyake, T Kakiuchi: "Irradiation up-regulates CD80 expression through induction of tumor necrosis factor-a and CD40 ligand expression on B lymphoma cells"Immunology. 106. 354-362 (2002

F Ishikawa、H Nakano、A Seo、Y Okada、H Torihata、Y Tanak、T Uchida、H Miyake、T Kakiuchi：“辐射通过诱导 B 淋巴瘤细胞上的肿瘤坏死因子-a 和 CD40 配体表达来上调 CD80 表达

垣内史堂,中野英樹: "末梢リンパ組織形成におけるリンフォトキシン(LT)、BLCケモカイン、SLCケモカイン"Annual Review免疫2001. 229-236 (2000)

Shido Kakiuchi、Hideki Nakano：“外周淋巴组织形成中的淋巴毒素 (LT)、BLC 趋化因子和 SLC 趋化因子”年度免疫学评论 2001. 229-236 (2000)

Y Iwasaki et al.: "Vasoactive intestinal peptide influences neurite out growth in cultured rat spinal cord neurons."Neurol Res, 23. 851-854 (2001)

Y Iwasaki 等人：“血管活性肠肽影响培养的大鼠脊髓神经元中的神经突生长。”Neurol Res，23. 851-854 (2001)