Evidence against epitope spreading of T cells in autoimmune diseases.

自身免疫性疾病中 T 细胞表位扩散的证据。

• 批准号: 14370161
• 负责人: YAMAMOTO Kazuhiko
• 金额: $ 9.28万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 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-14370161/
• 关键词: autommune disease; epitope; T cells; T cell receptor; pathogenic T cell; T細胞クローン

Epitope spreading is a well known phenomenon of autoimrnune process especially in the induction phase of the diseases. We examine whether this phenomenon is also working in the stage of advanced phase of autoimmune disorders. We have examined accumulated T cells clones in the several organs of spontaneous models of autoimmune disorders by RT PCR/SSCP analysis of T cell receptor. We found that there are extensive accumulations of T cells in the lesions of late phase animals and the same clones exist in the different pathological lesions of kidney, lung and central nervous system of such animals. We then constructed cDNA library from a single cell isolated from the lesions and obtained fill length cDNAs encoding alpha and beta chains of T cell receptor. After identification of the in vivo accumulated clones to the cloned T cell receptors, cytokine messages were examined using the cDNA library. Some clones were found to express interferon gamma message, suggesting that such clones were pathogenic T cells. We are now trying to reconstitute T cell receptor function by retroviral gene transfer in order to know the pathogenic properties of such clones.

抗原表位扩散是一种常见的自身免疫过程，尤其是在疾病的诱导阶段。我们研究这种现象是否也在自身免疫性疾病的晚期阶段工作。我们用T细胞受体的RT PCR/SSCP分析方法，检测了自发性自身免疫性疾病模型的几个器官中积累的T细胞克隆。结果发现，晚期动物的病变组织中有大量T细胞聚集，且在肾、肺和中枢神经系统的不同病变组织中存在相同的T细胞克隆。然后，我们从从病变中分离的单个细胞构建cDNA文库，并获得编码T细胞受体α和β链的全长cDNA。在鉴定克隆的T细胞受体的体内累积克隆后，使用cDNA文库检查细胞因子信息。发现一些克隆表达干扰素γ信息，表明这些克隆是致病性T细胞。我们现在正试图通过逆转录病毒基因转移来重建T细胞受体功能，以了解此类克隆的致病特性。

项目成果

Sekiya T.et al.: "Variations in the human Th2-specific chemokine TARC gene."Immunogenetics. 54. 742-745 (2003)

Sekiya T.等人：“人类 Th2 特异性趋化因子 TARC 基因的变异。”免疫遗传学。

Tahara H. et al.: "Reconstitution of CD8^+ T cells by retroviral transfer of the TCR αβ-chain genes isolated from a clonally expanded P815-infiltrating lymphocytes^1."J Immunol.. 171. 2154-2160 (2003)

Tahara H. 等人：“通过逆转录病毒转移从克隆扩增的 P815 浸润淋巴细胞中分离出的 TCR αβ 链基因来重建 CD8^+ T 细胞^1。”J 免疫学杂志 171. 2154-2160 (2003)

Tahara H.et al.: "Reconstitution of CD8^+ T cells by retroviral transfer of the TCR αβ-chain genes isolated from a clonally expanded P815-infiltrating lymphocyte."J Immunol.. 171. 2154-2160 (2003)

Tahara H. 等人：“通过逆转录病毒转移从克隆扩增的 P815 浸润淋巴细胞中分离的 TCR αβ 链基因来重建 CD8^+ T 细胞。”J 免疫学杂志 171. 2154-2160 (2003)

Takami K, Takuwa N, Okazaki H, Kobayashi M, Yamamoto K, etc.: "Interferon-γ inhibits hepatocycyte growth factor-simulated cell proliferation of human bronchial epithelial cells upregulation of p27^<kip1> cyclin-dependent kinase inhibitor."AM J Respir Cell

Takami K、Takuwa N、Okazaki H、Kobayashi M、Yamamoto K 等：“干扰素-γ 抑制肝细胞生长因子模拟的人支气管上皮细胞增殖，上调 p27^<kip1> 细胞周期蛋白依赖性激酶抑制剂。”AM呼吸细胞杂志

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