REGULATION OF INFLAMMATORY AND ALLERGY RESPONSES BY ANTI-LFA-1 MONOCLONAL ANTIBODY

抗 LFA-1 单克隆抗体对炎症和过敏反应的调节

• 批准号: 07670382
• 负责人: NISHIMURA Takashi
• 金额: $ 1.47万
• 依托单位: TOKAI UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670382/
• 关键词: Th1-Th2 balance; liver injury; allergy; LFA-1; T cells; IL-12; IgE; Cytokine; 炎症

In this project, we demonstrated that mouse liver injury model induced by propionibacterium acnes (P.acnes) plus LPS is T cell-dependent one judging from the experiment using T cell deficient nude mice. Because the liver injury was completely blocked by anti-LFA-1 mAb, LFA1-ICAM-1 interaction is essential for the activation and migration of effector cells to liver. It was also demonstrated that Th1-activating cytokine, IFN-gamma and IL-12 are key cytokines in this liver injury model. C57BL/6 mice, which are prone to show Th1 immunity, are sensitive to P.acnes plus LPS-induced liver injury, while BALB/c showing Th2 immunity are resistant to this. Therefore, genetically-controlled Th1/Th2 balance appeared to be important factor the induction of liver injury.The important role of LFA-1 molecule in allergy is also demonstrated from the evidence that anti-LFA-1 mAb administration inhibited IgE production in vivo for long-term.Thus, the important role of LFA-1 molecule and Th1-Th2 balances in the regulation of liver inflammatory responses and allergy was clearly demonstrated by this project.

本课题通过T细胞缺陷型裸鼠实验，证明痤疮丙酸杆菌（P.acnes）加LPS诱导的小鼠肝损伤模型是T细胞依赖性的。由于抗LFA-1单抗可完全阻断肝损伤，因此LFA 1-ICAM-1相互作用对于效应细胞的激活和向肝的迁移是必需的。还证明了Th 1活化细胞因子、IFN-γ和IL-12是该肝损伤模型中的关键细胞因子。C57 BL/6小鼠倾向于表现出Th 1免疫，对痤疮丙酸杆菌加LPS诱导的肝损伤敏感，而表现出Th 2免疫的BALB/c小鼠对此具有抵抗力。因此，遗传控制的Th 1/Th 2平衡似乎是诱导肝损伤的重要因素。LFA-1分子在变态反应中的重要作用也从抗LFA-1 mAb给药长期抑制体内IgE产生的证据中得到证实。因此，LFA-1分子和Th 1-该项目清楚地证明了肝脏炎症反应和过敏反应调节中的Th 2平衡。

项目成果

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Sato.N 等人：“Ly-6C^ NK1.1^ 细胞的功能表征”Immunol.Letters。

Tanaka, Y.et al.: "Productive and lytic infection of human CD4_+ type 1 helper T cells with macrophage-tropic human immunodeficiency virus type 1." J.Virol. 71. 465-470 (1977)

Tanaka, Y.等人：“1 型嗜巨噬细胞人类免疫缺陷病毒对人类 CD4_ 1 型辅助 T 细胞的生产性和裂解性感染。”

Nishimura,T.et al.: "The application of IL-12 to cytokine and gene therapy of tumor." Ann.NY.Acad.Sci.795. 375-378 (1996)

Nishimura,T.et al.：“IL-12 在肿瘤细胞因子和基因治疗中的应用。”

Nishimura, T.et al.: "The application of IL-12 to cytokine and gene therapy of tumor." Ann.NY.Acad.Sci.795. 375-378 (1996)

Nishimura, T.et al.：“IL-12 在肿瘤细胞因子和基因治疗中的应用。”

Nishimura, T.et al.: "The therapeutic effect of IL-12 or its antagonist in transplantation immunity." Ann.NY.Acad.Sci.795. 371-374 (1996)

Nishimura, T.et al.：“IL-12 或其拮抗剂在移植免疫中的治疗作用。”