Functional analysis of auto-reactive T cell clones in idiopathic thrombacytopenic purpura

特发性血小板减少性紫癜自身反应性T细胞克隆的功能分析

• 批准号: 18591069
• 负责人: HATO Takaaki
• 金额: $ 2.48万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591069/
• 关键词: platelet; idiopathic thrombocytopenic immure; mteerin; GPTTh-Tira; talin; T細胞

To explore the interaction between dendritic cells/T cells and the platelet membrane protein, GPIIb-IIIa, we established T cell clones recognizing the GPIIb amino acid sequences from patients with idiopathic thrombocytopenic purpura (ITP). These clones were composed of CD4+ helper T cells and CD8+ cytotoxic T cells. The HP patients with CD8+ T cell clones showed lower number of megakaryocytes in bone marrow, as compared with patients with CD4+ helper T cell clones. This finding suggests that CD8+ cytotoxic T cells destruct autologous platelets in some ITP patients. Platelet destruction in ITP has been believed to be mediated by autoantibody. Our results suggest T cell-mediated cytotoxicity is an alternative mechanism for platelet destruction in a subset of ITP and that different autoimmune-mediated mechanisms are involved in pathogenesis of ITP.We also examined structure and function of the GPIIb-IIIa molecule by using an expression system for mutated recombinant GPIIb -Ma on the surface of mammalian cells. We identified amino acids critical for regulation of GPIIb-IIIa activation in a certain loop of extracellular domain of GPIIIa. Moreover, we found two amino acids critical for regulation of GPIIb-IIIa activation in the cytoplasmic domain of GPIIIa and that these two residues cooperatively regulate talin-mediated GPIIb-IIIa activation.

为了探索树突状细胞/T细胞与血小板膜蛋白GPIIb- iiia之间的相互作用，我们建立了识别特发性血小板减少性紫癜（ITP）患者GPIIb氨基酸序列的T细胞克隆。这些克隆由CD4+辅助性T细胞和CD8+细胞毒性T细胞组成。与CD4+辅助T细胞克隆的患者相比，CD8+ T细胞克隆的HP患者骨髓中巨核细胞数量较少。这一发现表明CD8+细胞毒性T细胞破坏一些ITP患者的自体血小板。ITP的血小板破坏被认为是由自身抗体介导的。我们的研究结果表明，T细胞介导的细胞毒性是ITP子集中血小板破坏的另一种机制，并且不同的自身免疫介导机制参与了ITP的发病机制。我们还利用突变重组GPIIb -Ma在哺乳动物细胞表面的表达系统检测了GPIIb- iiia分子的结构和功能。我们在GPIIIa胞外结构域的某个环中确定了对GPIIb-IIIa活化调节至关重要的氨基酸。此外，我们在GPIIb-IIIa的细胞质域中发现了两个对GPIIb-IIIa活化调节至关重要的氨基酸，这两个残基协同调节talin介导的GPIIb-IIIa活化。

项目成果

ヒト細包傷害性T細胞が認識するAurora-A由来エピトープの同定

人类细胞毒性 T 细胞识别的 Aurora-A 衍生表位的鉴定

• 发表时间: 2007
• 作者: 越智 俊元;他
• 通讯作者: 他

Cooperative role of the membrane-proximal and distal residues of the integrin?3 cytoplasmic domain in regulation of talin-mediated?IIb?3 activation

整合素 3 胞质结构域的膜近端和远端残基在调节踝蛋白介导的 IIb 3 激活中的协同作用

• 发表时间: 2008
• 期刊: Journal of Biological Chemistry 283
• 作者: Hato T;et. al.
• 通讯作者: et. al.

Cappucino mutation in an autoimmune-prone strain of mice suggests a role of platelet function in the progression of immune complex crescentic elomerulonenhritis

易发生自身免疫的小鼠品系中的卡布奇诺突变表明血小板功能在免疫复合物新月体肾小球肾炎的进展中发挥作用

• 发表时间: 2006
• 期刊: Arthritis and Rheumatism 54
• 作者: Yoshida;M;Saiga;K;Hato;T;Iwaki;S;Niiya;T;Arita;N;Komori;H;Tsubaki;T;Furukawa;H;Terada;M;Maeyama;K;Nemoto;K;Nose;M;Ono;M
• 通讯作者: M

A novel monitoring of anti-platelet function of cilosmzel

西洛姆泽抗血小板功能的新型监测

• 发表时间: 2007
• 作者: Yamanouchi;J;et. al.
• 通讯作者: et. al.

The role of EHZF in erythroid differentiation

EHZF 在红细胞分化中的作用

• 发表时间: 2007
• 作者: Matsubara;E;et. al.
• 通讯作者: et. al.