Molecular mechnisms of immune tolerance.

免疫耐受的分子机制。

• 批准号: 05272102
• 负责人: HIRANO Toshio
• 金额: $ 145.15万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05272102/
• 关键词: lymphocyte lineage; signal transduction; tolerance; antigen receptor; cytokine; apoptosis; costimulatory factor; 骨髄ストローマ; サイトカイン受容体; 補助因子受容体; リンパ球初期分化; クローナル除去

Using a serum independent pro-B cell cultivation method, the Nishikawa group discovered the important role of fyn kinase in the formation of the (fusion line). In addition, this group showed the use of Flk2 expression as a marker for definition of the most undifferentiated stage of pro-B cells. Along with demonstrating that differentiated thymic cells (c-kit+, CD44+, CD25-) can be divided into FcR+ and FcR- groups, the Katsura group showed that T cell lineage cells are definitively FcR+. The Sugamura group developed IL-2 receptor gamma chain mutant mice. The gamma chain mutant mice showed severe immunodeficiency due to a reduction in B and T lineage cells and a complete lack of NK cells. The Hirano group, demonstrated the participation of the JAK-STAT transduction pathway in IL-6 receptor-mediated signal transduction. In addition, this group demonstrated the critical role of STAT3 in IL-6 mediated macrophage cell division. The Saito group, using a mouse line developed by crossing a CD3 deficient mouse and a TCR-Tg mouse, demonstrated the relationship between TCR signal strength and T cell selection. Also, they demonstrated the importance of Jak3 in T cell proliferation. In addition to demonstrating the importance of p52 in /VpreB/ signal transduction in B cells, the Sakaguchi group also solved the structure of this newly discovered molecule. The Suda group reported the strong expression of FAS in fetal spleen cells as well as the expression of functional FAS on B cells due to LPS stimulation, thus demonstrating the role of Fas in the death of activated B cells. Also, this group demonstrated that, due to protein degradation of membrane-bound human Fas ligand, Fas can be secreted while maintaining its cytotolytic activity. Furthermore, the group developed a monoclonal specific for Fas ligand and established an ELISA assay for Fas ligand expression.

Nishikawa小组利用不依赖血清的pro-B细胞培养方法，发现fyn激酶在融合系形成中的重要作用。此外，该组显示使用Flk 2表达作为定义pro-B细胞的最未分化阶段的标志物。沿着证明分化的胸腺细胞（c-kit+、CD 44+、CD 25-）可分为FcR+和FcR-组，Katrina组显示T细胞谱系细胞明确为FcR+。Sugamura小组开发了IL-2受体γ链突变小鼠。γ链突变小鼠由于B和T谱系细胞的减少和NK细胞的完全缺乏而表现出严重的免疫缺陷。Hirano小组证明了JAK-STAT转导通路参与IL-6受体介导的信号转导。此外，该研究小组还证明了STAT 3在IL-6介导的巨噬细胞分裂中的关键作用。Saito小组使用通过将CD 3缺陷小鼠和TCR-Tg小鼠杂交而开发的小鼠系，证明了TCR信号强度和T细胞选择之间的关系。此外，他们证明了Jak 3在T细胞增殖中的重要性。除了证明p52在B细胞中/Vpre B/信号转导中的重要性外，Sakaguchi小组还解决了这一新发现分子的结构。苏达研究组报道了胎脾细胞中FAS的强表达以及由于LPS刺激而在B细胞上功能性FAS的表达，从而证明了Fas在活化的B细胞死亡中的作用。此外，该小组证明，由于膜结合的人Fas配体的蛋白质降解，Fas可以分泌，同时保持其细胞溶解活性。此外，该小组开发了特异性Fas配体的单克隆抗体，并建立了Fas配体表达的ELISA测定法。

项目成果

Yamanaka Y,et al.: "Differentiation and growth arrest sifnals generate through the cytoplasmic region of gp 130 that is essential for Stat3 activation." EMBO J.(in press).

Yamanaka Y 等人：“分化和生长停滞信号通过 gp 130 的细胞质区域产生，这对于 Stat3 激活至关重要。”

Inui S,.et al.: "Molecular cloning of a cDNA clone encoding a phosphoprotein component related to the immunoglobulin receptor (IgR)-mediated signal transduction." J.Immunol.154. 2714-2723 (1995)

Inui S,.et al.：“编码与免疫球蛋白受体 (IgR) 介导的信号转导相关的磷蛋白成分的 cDNA 克隆的分子克隆。”

Yasunaga M.: "Involvement of Fyn tyrosine kinase in progression of cytokinesis of B lymphocyte progenitor." J.Cell Biol.132. 1-9 (1996)

Yasunaga M.：“Fyn 酪氨酸激酶参与 B 淋巴细胞祖细胞胞质分裂的进展。”

Tanaka M.: "Expression of the functional soluble form of human Fas ligand in activated lymphocytes." EMBO J.14. 1129 (1995)

Tanaka M.：“人 Fas 配体的功能性可溶形式在活化淋巴细胞中的表达。”

Dou,Y-M.,Katsura,Y.,et al.: "A novel culture system for induction of T cell development: Modification of fetal thymus organ dulrure." Thymus. 23. 195-207 (1995)

Dou,Y-M.,Katsura,Y.,et al.：“诱导 T 细胞发育的新型培养系统：胎儿胸腺器官硬质的修饰。”