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Research on cytotoxic T cell responses to hepatitis C virus infection

细胞毒性T细胞对丙型肝炎病毒感染反应的研究

基本信息

批准号：
14370190
负责人：
IMAWARI Michio
金额：
$ 7.1万
依托单位：
Showa University (2003-2004)Jichi Medical University (2002)
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 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370190/
关键词：
hepatitis C virus cytotoxic T cell interferon epitope HLA-A24

项目摘要

Hepatitis C virus (HCV) infection frequently persists, and leads to chronic hepatitis, cirrhosis, and eventually hepatocellular carcinoma. Acute HCV infection has decreased dramatically after universal use of disposable medical instruments and introduction of HCV test for blood products. Elimination of HCV from chronic hepatitis C patients became possible by interferon therapies. However there are still many patients who do not respond to the therapy. Since cytotoxic T lymphocytes (CTL) play an important role in elimination of infected viruses, the therapy that augments HCV-specific CTL responses may be effective for such patients. We developed the system that assesses CTL responses of peripheral blood to whole HCV antigens. Using the system, we found that HCV-specific CTL responses of patients treated with interferon decreased in accord with the decrease of HCV in serum, and that a temporary interruption of the therapy augmented CTL responses by stimulation with re-appeared HCV. We also attempted to identify HCV-specific CTL epitopes as many as possible for future development of HCV peptide vaccines. Using HCV peptides with HLA-A24-binding motif or overlapping peptides encompassing the whole HCV protein, we identified 16 novel HCV-specific CTL epitopes by interferon-', ELISpot assay. We also analyzed the phenotypes of HCV-specific CTL using CTL epitope peptide-HLA-A24-Ig dimers and cell surface markers, and found that HCV-specific CTL in the peripheral blood were poorly activated and differentiated variously.

丙型肝炎病毒（HCV）感染经常持续，并导致慢性肝炎、肝硬化，最终导致肝细胞癌。在一次性医疗器械的普遍使用和对血液制品进行丙型肝炎病毒检测后，急性丙型肝炎病毒感染显著减少。干扰素治疗可以消除慢性丙型肝炎患者的丙型肝炎病毒。然而，仍有许多患者对治疗没有反应。由于细胞毒性T淋巴细胞（CTL）在消除感染病毒中起着重要作用，因此增强hcv特异性CTL反应的治疗可能对此类患者有效。我们开发了评估外周血对整个HCV抗原CTL反应的系统。使用该系统，我们发现使用干扰素治疗的患者的HCV特异性CTL反应与血清中HCV的降低一致下降，并且暂时中断治疗可以通过重新出现的HCV刺激增强CTL反应。我们还试图尽可能多地鉴定HCV特异性CTL表位，以便将来开发HCV肽疫苗。利用具有hla - a24结合基序的HCV肽或覆盖整个HCV蛋白的重叠肽，我们通过干扰素-' （ELISpot）检测鉴定了16个新的HCV特异性CTL表位。我们还利用CTL表位肽- hla - a24 - ig二聚体和细胞表面标记物分析了hcv特异性CTL的表型，发现外周血中hcv特异性CTL活化程度低，分化程度不同。