Mechanisms of the anergy of T cells induced by varient types of soluble VCAM-1

不同类型可溶性VCAM-1诱导T细胞无反应性的机制

• 批准号: 09670483
• 负责人: MATSUYAMA Takami
• 金额: $ 1.73万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670483/
• 关键词: Soluble VCAM-1; Intracellular Signals; IL-2 Nuclear Factors; Calmodulin dependent kinase II; Chemotaxis; シグナル伝達; 自己免疫; アネルギー; カルモデュリンキナーゼ; 関節液; IL-2

1. We examined how soluble VCAM-1 affects the pathway of signal transduction in Jurkat cells induced by the stimulation of TCR/CD3 molecules.1) Addition of soluble VCAM-1 to stimulated Jurkat cells inhibited the binding of Ap-1, NF-AT and Oct-I to the IL-2 promotor region but not that of NF-kB.2) Soluble VCAM-1 induced the activity of calmodulin dependent kinase II but not the phosphorylation of focal adhesion molecule in stimulated Jurkat cells.3) The chemotaxis of T cells by soluble VCAM-1 was dependent on the activity of rho, protein kinase C, and calmodulin dependent kinase II.2. Previously, we reported that soluble VCAM-1 acts inhibitory on the functions of T cells. In the present experiments, it was fount that soluble VCAM-1 play the following roles in the functions of T cells.1) Soluble VCAM-1 inhibited the function of CD45RO^+ T cells as compared that of CD45RO^- T cells.2) Soluble VCAM-1 induced the chemotaxis of IL-2 dependent T cell lines, synovial fluid T cells from rheumatoid arthritis patients and Jurkat cells.3. We developed a dimer form of soluble VCAM-1 by connecting cDNA of soluble VCAM-1 with cDNA of IgGFc portion.

1.我们研究了可溶性VCAM-1如何影响由TCR/CD 3分子刺激诱导的Jurkat细胞中的信号转导途径。1）向刺激的Jurkat细胞中加入可溶性VCAM-1抑制了Ap-1的结合，NF-AT和Oct-I与IL-2启动子区结合，但不与NF-kB结合。1诱导受刺激的Jurkat细胞中钙调素依赖性激酶II的活性，但不诱导黏着斑分子的磷酸化。3）可溶性VCAM-1对T细胞的趋化作用依赖于rho的活性，蛋白激酶C和钙调蛋白依赖性激酶II.2。此前，我们报道了可溶性VCAM-1对T细胞的功能具有抑制作用。本实验发现可溶性VCAM-1在T细胞功能中具有以下作用：1）可溶性VCAM-1对CD 45 RO ^+ T细胞功能的抑制作用优于对CD 45 RO ^- T细胞功能的抑制作用; 2）可溶性VCAM-1对IL-2依赖性T细胞系、类风湿关节炎患者滑液T细胞和Jurkat细胞的趋化性有诱导作用.我们通过将可溶性VCAM-1的cDNA与IgGFc部分的cDNA连接，开发了可溶性VCAM-1的二聚体形式。

项目成果

Atsushi Kitani, Noriko Nakashima, Tomomaro Izumihara, Masaki Inagaki, Baohui Xu, Su Yu, Takemasa Matsuda, and Takami Matsuyama: "Soluble VCAM-1 induces chemotaxis of Jurkat and synovial fluid T cells bearing high affinity very late antigen-4." J.Immunol.1

Atsushi Kitani、Noriko Nakashima、Tomomaro Izumihara、Masaki Inagaki、Baohui Xu、Su Yu、T​​akemasa Matsuda 和 Takami Matsuyama：“可溶性 VCAM-1 诱导具有高亲和力极晚期抗原 4 的 Jurkat 和滑液 T 细胞的趋化性。”

Yns,et al.: "Puthological significunu of elevated soluble CO14 production in sheumatad anthty" Rheumatal International. (in press).

Yns 等人：“sheumatad anthty 中可溶性 CO14 产量升高的Puthological senseunu”Rheumatal International。

Kitani A et al.: "Soluble VCAM-1 induces chemotaxis of Jurkat and synovial fluid T cells bearing high offinity very late antigen-4." J.Immunol.161. 4931-4938 (1998)

Kitani A 等人：“可溶性 VCAM-1 诱导带有高亲和性极晚期抗原 4 的 Jurkat 和滑液 T 细胞的趋化性。”

Kitani A.他: "Soluble VCAM-1 induces chemotaxis of Jurkat and Synorial fluid Tcells bearing high ffinity very late antigen-4." J.Immunal.161. 4931-4938 (1998)

Kitani A. 等人：“可溶性 VCAM-1 诱导具有高亲和力极晚期抗原 4 的 Jurkat 和 Synorial 液 T 细胞的趋化性。”J.Immunal.161 (1998)。

XuB,Aoyama K,Kitani A et al.: "Interleukin-12 enhanus contact hypersensitivity by modulating the in vivo cytokine pattern in mice" J.Interferone and Cytokine Research. 18. 23-31 (1998)

XuB、​​Aoyama K、Kitani A 等人：“通过调节小鼠体内细胞因子模式来实现白介素 12 enhanus 接触超敏反应”J.Interferone and Cytokine Research。