Analysis of cellular immune responses in perihperal blood and liver tissues in HCV infection

HCV感染后外周血和肝组织细胞免疫反应分析

基本信息

批准号：
11470136
负责人：
IMAWARI Michio
金额：
$ 3.01万
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 (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470136/
关键词：
hepatitis C virus immunology helper T cell cytotoxic T lymphocyte interferon-γ interleukin-4 interleukin-10 ELISpot C型肝炎 HCV抗原 C型肝炎ウイルスコア蛋白 C型肝炎ウイルスNS3蛋白

项目摘要

Hepatitis C virus (HCV) infection frequently persists, progresses to chronic hepatitis and cirrhosis, and finally develops hepatocellular carcinoma. Although viruses in the infected cells are eliminated by virus-specific cytotoxic T lymphocytes (CTLs) that recognize endogenously synthesized, processed viral proteins presented by HLA and lyse the cells, the CTL responses are regulated by helper T cells and immunomodulatory cytokines. In the present study, we investigated mainly the helper T cell and immunomodulatory cytokine responses in peripheral blood ant liver tissues of patients with chronic HCV infection. In chronic HCV infection, type 1 helper T cell responses that produced interferon-γin response to HCV proteins dominated type 2 helper T cell responses that produced interleukin-4. However, HCV proteins stimulated the production of immunosuppressive interleukin-10. In the peripheral blood of patients with chronic hepatitis C, the number of HCV-stimulated interleukin-10-producing cells was larger than that of HCV-stimulated interferon-γ-producing cells. Thus, the anti-HCV responses seemed to be suppressed in the peripheral blood. HCV-specific helper T cells were concentrated in the liver tissues. The number of HCV-stimulated interferon-γ-producing cells in the peripheral blood was inversely correlated with serum HCV RNA levels. Interferon treatment decreased the number of peripheral blood HCV-stimulated interferon-γ-producing cells at 3 month, but the number returned to the pretreatment level later. There were regions in HCV proteins that stimulated of production of interferon-γ and interleukin-10 by peripheral blood mononuclear cells of patients with chronic HCV infection in common. Finally we identified an epitope in HCV recognized by CTLs in association with HLA-A^*0206.

丙型肝炎病毒（HCV）感染经常持续存在，发展为慢性肝炎和肝硬化，最终发展出肝细胞癌。尽管感染细胞中的病毒被病毒特异性的细胞毒性T淋巴细胞（CTL）消除，该病毒识别由HLA和细胞呈现的内源合成，加工病毒蛋白的内源性病毒蛋白，但CTL反应受Helper T细胞和免疫抑制性细胞膜调节。在本研究中，我们主要研究了慢性HCV感染患者的外周血肝脏肝脏中的辅助T细胞和免疫调节细胞因子反应。在慢性HCV感染中，产生干扰素-γIN对HCV蛋白的反应的1型辅助T细胞反应主导了产生白介素-4的2型辅助T细胞反应。但是，HCV蛋白刺激了免疫抑制白细胞介素10的产生。在患有慢性丙型肝炎患者的外周血中，HCV刺激的白介素-10产生的细胞的数量大于HCV刺激的白介素 - γ产生细胞的细胞。这，抗HCV反应似乎在外周血中受到抑制。 HCV特异性辅助T细胞浓缩在肝组织中。外周血中HCV刺激的白细胞介素-γ产生细胞的数量与血清HCV RNA水平成反比。干扰素治疗在3个月时出现了外周血HCV刺激的干扰素产生细胞的数量，但后来的数量恢复到了预处理水平。 HCV蛋白中有一些区域通过外周血单核细胞刺激了慢性HCV感染患者的外周血单核细胞的产生。最后，我们确定了CTL与HLA-A^*0206相关的HCV中的一集。