Regulatory mechanism of homeostatic T cell proliferation

稳态T细胞增殖的调控机制

• 批准号: 14599011
• 负责人: OHTEKI Toshiaki
• 金额: $ 2.3万
• 依托单位: AKITA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14599011/
• 关键词: CTLA-4; IL-2; IL-2R; T cell activation; autoimmune disease; human; mouse; 活性化T細胞; B7; IL-15; 抗原特異的; in vivo; ホメオスターシス増殖

Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) transduces inhibitory signals for T cell activation and regulates T cell homeostasis in vivo. Indeed, mice deficient for CTLA-4 exhibit lymphoproliferative autoimmune disease and early death at 3-4 wk of age. We show that T cells activated in the absence of IL-2/IL-2R interaction fail to express CTLA-4 on the cell surface. The lack of surface expression is due to impaired mRNA expression but not to a defect in protein trafficking. Our results demonstrate that IL-2 is essential for CTLA-4 induction in activated T cells, and suggest that the impairment of CTLA-4 induction is one of mechanisms causing fatal autoimmune disease observed in mice lacking IL-2/IL-2R system in vivo.

细胞毒性T淋巴细胞相关分子-4（CTLA-4）在体内转导T细胞活化的抑制信号并调节T细胞稳态。事实上，CTLA-4缺陷的小鼠在3-4周龄时表现出淋巴增生性自身免疫性疾病和早期死亡。我们表明，在IL-2/IL-2 R相互作用的情况下激活的T细胞不能在细胞表面上表达CTLA-4。表面表达的缺乏是由于mRNA表达受损，而不是蛋白质运输缺陷。我们的研究结果表明，IL-2是必需的CTLA-4的诱导活化的T细胞，并建议CTLA-4的诱导功能障碍是导致致命的自身免疫性疾病的机制之一，在缺乏IL-2/IL-2 R系统的小鼠体内观察。

项目成果

Honda, K.: "Selective contribution of IFN-α/β signaling to the maturation of dendritic cells induced by double-stranded RNA or viral infection."Proc.Natl.Acad.Sci.USA. 100. 10872-10877 (2003)

Honda, K.：“IFN-α/β 信号对双链 RNA 或病毒感染诱导的树突状细胞成熟的选择性贡献。”Proc.Natl.Acad.Sci.USA 100. 10872-10877 (2003)。

樗木俊聡: "IL-15による樹状細胞機能の調節"蛋白質・核酸・酵素. 47. 2139-2144 (2002)

Toshisato Kuraki：“IL-15 对树突状细胞功能的调节”蛋白质/核酸/酶。 47. 2139-2144 (2002)

Murata, Y.: "IFN-γ and pro-inflammatory cytokine production by antigen presenting cells is dictated by intracellular thiol redox status regulated by oxygen tention"Eur. J. Immunol.. 32(10). 2866-2873 (2002)

Murata，Y.：“抗原呈递细胞产生的IFN-γ和促炎细胞因子是由氧张力调节的细胞内硫醇氧化还原状态决定的”Eur.J.Immunol.. 2866-2873(2002)。

Yamauchi, T., Kamon, J., Ito, Y., Tsuchida, A., Yokomizo, T., Kita, S., Sugiyama, T., Miyagishi, M., Hara, K., Tsunoda, M., Murakami, K., Ohteki, T., Uchida, S., Takekawa, S., Waki, H., Tsuno, N.H., Shibata, Y., Terauchi, Y., Froguel, P., Tobe, K., Koyasu

山内 T.、嘉门 J.、伊藤 Y.、土田 A.、横沟 T.、北 S.、杉山 T.、宫岸 M.、原 K.、角田 M.、

Murata, Y., Ohteki, T., Koyasu, S., Hamuro, J.: "IFN-γ and pro-inflammatory cytokine production by antigen presenting cells is dictated by intracellular thiol redox status regulated by oxygen tention."Eur.J.Immunol.. 23. 2866-2873 (2002)

Murata, Y.、Ohteki, T.、Koyasu, S.、Hamuro, J.：“抗原呈递细胞产生的 IFN-γ 和促炎细胞因子是由氧滞留调节的细胞内硫醇氧化还原状态决定的。”Eur.J .免疫学.. 23. 2866-2873 (2002)