Establishment of antigen-specific regulatory T cell lines induced by oral tolerance and the application to immunotherapy

口服耐受诱导抗原特异性调节性T细胞系的建立及其在免疫治疗中的应用

• 批准号: 12470113
• 负责人: YAMAMOTO Kazuhiko
• 金额: $ 9.92万
• 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: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470113/
• 关键词: Oral tolerance; T cells; IL-10; Peyer's patch; dendritic cells

Oral tolerance is one of the promising methods for immunotherapy. Regulatory T cells generated by the orally administered antigens would be the most responsible cell population for the suppressive action. In order to establish regulatory T cell lines, it is important to know the mechanisms of the regulation as well as the conditions to generate these T cells. We thus establish an assay system to monitor the suppressive activity to the ongoing immune-response by mixing the candidate regulatory cells with antigen-specific splenocytes. We next focused on the Th3/Tr1 cells which secrete TGF-beta because this cells is one of the most well characterized regulatory cells. We have thus characterize the several culture conditions to generate Th3/Tr1 cells. Spleen cells from OVA specific TCR transgenic mice were cultured in different conditions and resultant OVA specific cells were assayed for the secretion of TGF-beta or the above established evaluation system. We are now narrowing down suitable conditions for the generation of regulatory cells.

口服耐受是免疫治疗的一种有前途的方法。由口服给予的抗原产生的调节性T细胞将是对抑制作用最负责的细胞群。为了建立调节性T细胞系，重要的是了解调节的机制以及产生这些T细胞的条件。因此，我们建立了一个测定系统，通过将候选调节细胞与抗原特异性脾细胞混合来监测对正在进行的免疫应答的抑制活性。我们接下来关注分泌TGF-β的Th 3/Tr 1细胞，因为该细胞是最充分表征的调节细胞之一。因此，我们已经表征了产生Th 3/Tr 1细胞的几种培养条件。在不同条件下培养来自OVA特异性TCR转基因小鼠的脾细胞，并测定所得OVA特异性细胞的TGF-β分泌或上述建立的评价系统。我们现在正在缩小产生调节细胞的合适条件。

项目成果

Kurokawa M. Tong J. Matsui T. Masuko-Hongo K. Yabe T. Nishikawa K. Yamamto K. Kato T.: "Paired cloning of the T cell receptor α and β genes from a single T cell without the establishment of a T cell clone"Clin. Exp. Immunol.. 123. 340-345 (2000)

Kurokawa M. Tong J. Matsui T. Masuko-Hongo K. Yabe T. Nishikawa K. Yamamto K. Kato T.：“从单个 T 细胞配对克隆 T 细胞受体 α 和 β 基因，无需建立 T细胞克隆“Clin.Exp.Immunol..123.340-345(2000)

Setoguchi K.: "Peroxisome proliferator-activated receptor-r haploinsufficiency enhances B cell proliferative responses and exacerbates experimentally induced arthritis"J.Clin.Invest.. 108. 1667-1675 (2001)

Setoguchi K.：“过氧化物酶体增殖物激活受体-r 单倍体不足增强 B 细胞增殖反应并加剧实验诱导的关节炎”J.Clin.Invest.. 108. 1667-1675 (2001)

Yamamoto K.: "T cell and autoimmune diseases"Allergy International. 50. 1-4 (2001)

Yamamoto K.：“T 细胞和自身免疫性疾病”过敏国际。

Sawabe T.: "Accumulation of common clonal T Cells in multiple lesions of sarcoidosis"Mol. Med.. 6. 793-802 (2000)

Sawabe T.：“结节病多处病变中常见克隆 T 细胞的积累”Mol。

Yamada R. Tanaka T. Unoki K. Nagai T. Sawada T. Ohnishi Y. Tsunoda T. Yukioka M. Maeda A. Suzuki K. Tateishi H. Ochi T. Nakamura Y. and Yamamoto K.: "Association between a single-nucleotide polymorphism in the promoter of the human interleukin-3 gene and

Yamada R. Tanaka T. Unoki K. Nagai T. Sawada T. Ohnishi Y. Tsunoda T. Yukioka M. Maeda A. Suzuki K. Tateishi H. Ochi T. Nakamura Y. 和 Yamamoto K.：“单-之间的关联