Induction of auto-antigen reactive T cell clone from naive T cells in patients with primary biliary cirrhosis using lymphoid dendritic cells.

使用淋巴树突状细胞从原发性胆汁性肝硬化患者的初始 T 细胞中诱导自身抗原反应性 T 细胞克隆。

• 批准号: 09670553
• 负责人: MASUMOTO Toshikazu
• 金额: $ 1.98万
• 依托单位: Ehime University School
• 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-09670553/
• 关键词: primary biliary cirrhosis; lymphoid dendritic cell; pyruvate dehydrogenase; auto-reactive T cell; antigen-pulse; allogenic mixed leucocyte reaction; nitric oxide; naive T cell; Allogenic mixed leucocyte reaction; リンパ性幼惹化反応; 自己反応性T細胞フローン

I analyzed the function of lymphoid dendritic cells (DCs) in primary biliary cirrhosis (PBC) and tried to induce auto-antigen reactive T cell clone by using DCs. Stimulatory capacity of DCs from PBC patients in allogenic mixed leucocyte reaction (MLR) was significantly lower compared to normal controls and chronic hepatitis C patients. Cytokine and nitric oxide (NO) production in supernanant of allogenic MLR and DCs incubated with Staphylococcus aureus Cowan I strain (SAC) were mesured, and it was found that NO production was significant increased from DC culture in patients with PBC compared to normal controls. Addition of NO inhibitor (N^G-monomethyI-L-arginine monoacetate) to culture resulted in reduced NO production and recovery of reduced allogenic MLR in patients with PBC.DCs pulsed with pyruvate dehydrogenase (PDH) induced significant T cell proliferation in patients with PBC compared to normal controls. It was concluded that DCs might be useful to induce auto-reactive T cell clone by recovery of DCs dysfunction in patients with PBC.

本研究分析了原发性胆汁性肝硬化（PBC）中淋巴样树突状细胞（DC）的功能，并尝试利用DC诱导自身抗原反应性T细胞克隆。PBC患者DC刺激同种异体混合白细胞反应（MLR）的能力明显低于正常对照组和慢性丙型肝炎患者。检测同种异体MLR和DC与金黄色葡萄球菌科万I株（SAC）共培养上清液中细胞因子和一氧化氮（NO）的产生，发现PBC患者DC培养上清液中NO的产生较正常对照组显著增加。在培养液中加入NO抑制剂（N，G-单甲基-L-精氨酸单乙酸酯）可减少PBC患者的NO产生，并恢复减少的同种异体MLR。与正常对照相比，经丙酮酸脱氢酶（PDH）脉冲的DC可诱导PBC患者显著的T细胞增殖。结论：PBC患者DC功能障碍的恢复可能有助于DC诱导自身反应性T细胞克隆的形成。

项目成果

Masumoto T, Ninomiya T, Akbar SMF, et al: "Determination of the interleukin-2 receptor b chain by peripheral blood mononuclear cells in patients with primary biliary cirrhosis." Hepatology Research. 8. 207-214 (1997)

Masumoto T、Ninomiya T、Akbar SMF 等人：“原发性胆汁性肝硬化患者外周血单核细胞测定白细胞介素 2 受体 b 链。”

Yamamoto K,Masumoto T,et al.: "Increased nitric oxide (NO) production by antigen-presenting dendritic cells is responoible for low allogenic mixed leukocyte reaction(MLR)in primary biliary crrhosis(PBC)" Clin Exp Immunol. 114. 94-101 (1998)

Yamamoto K、Masumoto T 等人：“抗原呈递树突状细胞产生的一氧化氮 (NO) 增加是原发性胆汁性硬化 (PBC) 中低同种异体混合白细胞反应 (MLR) 的原因”Clin Exp Immunol。

Masumoto T,et al.: "Three patients with autoimmune cholangiopathy treated with predovisolone" J Gastroentevol. 33. 909-913 (1998)

Masumoto T 等人：“三名患有自身免疫性胆管病的患者接受泼维松龙治疗”J Gastroentevol。

Shinomiya M, Masumoto T, Nadano S, et al: "Lymphoid dendritic cells in the liver of patients with primary biliary cirrhosis and its mouse model." Hepatology Research. 11. 84-94 (1998)

Shinomiya M、Masumoto T、Nadano S 等人：“原发性胆汁性肝硬化患者肝脏中的淋巴树突状细胞及其小鼠模型。”

Masumoto T, et al.: "Three patients with autoimmune chalang opathy treated with predonisolone" J Gastroenterol. 33. 909-913 (1998)

Masumoto T 等人：“三名患有自身免疫性 chalang 病的患者接受泼尼松龙治疗”J Gastroenterol。