Pathogenesis of viral hepatitis based on intrahepatic immune response to hepatitis virus

基于肝炎病毒肝内免疫反应的病毒性肝炎发病机制

• 批准号: 15590692
• 负责人: KAKIMI Kazuhiro
• 金额: $ 2.3万
• 依托单位: The University of Tokyo (2004)Tokyo Medical University (2003)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590692/
• 关键词: hepatitis virus; HBV; CTL; chemokine; cytokine; B型肝炎ウイルス(HBV); 細胞傷害性T細胞(CTL)

The distribution and dynamics of the cytotoxic T lymphocyte (CTL) response to hepatitis B surface antigen (HBsAg) were studied in mice after intramuscular DNA immunization and after hepatic infection by a recombinant adenovirus that expresses the hepatitis B virus genome (Ad-HBV). CTLs specific for HBsAg accumulate preferentially in the spleen after DNA immunization but are primarily intrahepatic after Ad-HBV infection. The secondary CTL response to Ad-HBV in DNA-primed mice is characterized by rapid depletion of effector CTLs from the spleen, and their expansion in the liver where they cause hepatitis, secrete interferon gamma (IFNγ), and inhibit HBV gene expression. Together with intrahepatic IFNγ expression, CXCL9 and CXCL10 mRNAs were strongly induced in the liver. Suppression of HBsAg synthesis is accompanied by disappearance of intrahepatic IFNγ-producing CTLs and their reaccumulation in the spleen. The data suggest a possible explanation for the paucity and functional deficiency of HBV-specific CTLs in the periphery during chronic HBV infection, and that the severity of infection can be worsened by a preexisting CTL response if neutralizing antibody is not also present.

研究了小鼠肌肉DNA免疫和表达乙型肝炎病毒基因组（Ad-HBV）的重组腺病毒感染后，细胞毒性T淋巴细胞（CTL）对乙型肝炎表面抗原（HBsAg）的反应分布和动态。DNA免疫后，HBsAg特异性ctl优先在脾脏积聚，但在Ad-HBV感染后主要在肝内积聚。dna引物小鼠对Ad-HBV的继发性CTL反应的特征是脾脏中效应CTL的快速消耗，它们在肝脏中扩张，在那里它们引起肝炎，分泌干扰素γ (IFNγ)，并抑制HBV基因表达。与肝内IFNγ表达一起，CXCL9和CXCL10 mrna在肝脏中被强烈诱导。抑制HBsAg的合成伴随着肝内产生ifn - γ的ctl的消失及其在脾脏中的重新积聚。这些数据为慢性HBV感染期间外周HBV特异性CTL的缺乏和功能缺陷提供了可能的解释，并且如果不存在中和抗体，则先前存在的CTL反应可能会使感染的严重程度恶化。

项目成果

Depletion of CD25+CD4+T cells (Tregs) enhances the HBV-specific CD8+ T cell response primed by DNA immunization

• DOI: 10.3748/wjg.v11.i24.3772
• 发表时间: 2005-06-28
• 期刊: WORLD JOURNAL OF GASTROENTEROLOGY
• 影响因子: 4.3
• 作者: Furuichi, Yoshihiro;Tokuyama, Hirotake;Kakimi, Kazuhiro
• 通讯作者: Kakimi, Kazuhiro

Kazuhiro Kakimi: "Immune-based novel therapies for chronic hepatitis C virus infection."Human Cell. 16(in press). (2003)

Kazuhiro Kakimi：“基于免疫的慢性丙型肝炎病毒感染的新疗法。”人类细胞。

Differential dynamics of the peripheral and intrahepatic cytotoxic T lymphocyte response to hepatitis B surface antigen

• DOI: 10.1016/j.virol.2005.01.004
• 发表时间: 2005-03-15
• 期刊: VIROLOGY
• 影响因子: 3.7
• 作者: Isogawa, M;Kakimi, K;Chisari, FV
• 通讯作者: Chisari, FV

HBV関連遺伝子トランスジェニックマウスによるB型肝炎研究の最新動向

乙型肝炎相关基因转基因小鼠研究的最新趋势

• 发表时间: 2004
• 期刊: 日本臨床 62
• 作者: Furuichi;Y.他6名;垣見和宏
• 通讯作者: 垣見和宏

肝疾患とケモカイン

肝脏疾病和趋化因子

• 发表时间: 2004
• 期刊: Bio Clinica 19
• 作者: Fukuhara;S.;Suzuki;H.et al.;垣見和宏
• 通讯作者: 垣見和宏