Molecular and immunological study on the pathogenesis of hepatitis C

丙型肝炎发病机制的分子和免疫学研究

• 批准号: 07407015
• 负责人: IMAWARI Michio
• 金额: $ 8.13万
• 依托单位: Jichi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07407015/
• 关键词: hepatitis C; hepatitis C virus; cytotoxic T lymphocyte; HLA B44; epitope; perforin; Fas; TNF; ヘルパーT細胞; インターフェロンγ; インターロイキン4; 変異; パ-フォリン

In the present study, we demonstrated that HLA B44-positive hepatitis C patients with demonstarable CTL response to HCV core antigen a.a. 88-96 had lower levels of serum HCV RNA, suggesting that CTL may suppress the outgrowth of HCV.In addition, CTh response was observed to multiple HCV epitopes in the same patients. Thus CTL response to HCV infection is not strong enough to eliminate the virus.The variation of amino acid in HCV core a. a. 88-96 was observed only 3 of 27 HLA B44-positive patients. All three variants could be recognized by CTL as effectively as wild-type HCV antigen, but two of three variants could not induce CTL effectively while the other one could induce CTL.Furthermore, when a small amount of variant HCV co-existed with wild-type HCV, the induction of CTL recognizing spesifically variant epitope was sppressed.HCV-specific CTL recognized and killed HCV-infected target cells by perform-, Fas ligand-, and. TNF-based mechanisms. In addition, activated CTL killed bystander sensitive non-infected cells by Fas ligand and TNF-based mechanisms. The mechanisms may contribute to the expansion of inflammation in the liver.

在本研究中，我们证明了HLA B44阳性丙型肝炎患者对HCV核心抗原A.A.的CTL反应反应。 88-96的血清HCV RNA水平较低，这表明CTL可能抑制HCV的生长。加法，同一患者的多个HCV表位观察到CTH反应。因此，CTL对HCV感染的反应不足以消除病毒。HCV核心A中的氨基酸变化。一个。在27个HLA B44阳性患者中，只有88-96例观察到了38-96。 All three variants could be recognized by CTL as effectively as wild-type HCV antigen, but two of three variants could not induce CTL effectively while the other one could induce CTL.Furthermore, when a small amount of variant HCV co-existed with wild-type HCV, the induction of CTL recognizing spesifically variant epitope was sppressed.HCV-specific CTL通过性能，FAS配体识别并杀死了HCV感染的靶细胞。基于TNF的机制。此外，激活的CTL通过FAS配体和基于TNF的机制杀死了旁观者敏感的未感染细胞。该机制可能导致肝脏炎症的扩张。

项目成果

Ando,Kazuki: "Perforin,Fas/Fas Ligand,TNF-α pathways as specific and bystander killing mechanisms of hepatitis C virus-specific human CTL" Journal of Immunology. 158. 5283-5291 (1997)

Ando，Kazuki：“穿孔素、Fas/Fas 配体、TNF-α 途径作为丙型肝炎病毒特异性人类 CTL 的特异性和旁观者杀伤机制”《免疫学杂志》158. 5283-5291 (1997)。

Kita, Hiroto: "A minimal and optimul cytotoxic T cell epitope within hepatitis C virus nucleoprotein" Jpurnal of General Virology. 76. 3189-3193 (1995)

Kita, Hiroto：“丙型肝炎病毒核蛋白内的最小且最佳的细胞毒性 T 细胞表位”《普通病毒学杂志》。

Ando, Kazuki: "Perforin, Fas/Fas ligand, TNF-α pathways as specific and bystander killing mechanisms of hepatitis C virus-specific human CTL" Journal of Immunology. 5283-5291 (1997)

Ando, Kazuki：“穿孔素、Fas/Fas 配体、TNF-α 途径作为丙型肝炎病毒特异性人类 CTL 的特异性和旁观者杀伤机制”《免疫学杂志》5283-5291 (1997)。

Hiroishi,Kazumasa: "Cytotoxic T lymphocyte response and viral load in hepatitis C virus infection" Hepatology. 25(印刷中). (1997)

Hiroishi, Kazumasa：“丙型肝炎病毒感染中的细胞毒性 T 淋巴细胞反应和病毒载量”《肝病学》25（出版中）。

Michio Imawari: "Th1 and Th2 imbalance in chronic hepatitis C" Journal of Gastroenterology. 33. 602-603 (1998)

Michio Imawari：“慢性丙型肝炎中 Th1 和 Th2 失衡”胃肠病学杂志。