Iken Khadija, Huang Lin, Bekele Hewan, Schmidt Emmett V, Koziel Margaret James
Division of Infectious Disease, Beth Israel Deaconess Hospital, HIM 223a, 330 Brookline Ave., Boston, MA 02115, USA.
Virology. 2006 Mar 15;346(2):363-72. doi: 10.1016/j.virol.2005.11.017. Epub 2005 Dec 5.
A central unresolved issue in hepatitis C virus (HCV) infection is how the virus establishes chronic infection. Recent studies suggest that the liver microenvironment leads to apoptosis of activated T cells, which may be involved in the tolerance to liver allograft. Here, We report that murine hepatocytes expressing a transgene encoding the HCV structural proteins core, envelope 1 (E1) and envelope 2 (E2) enhance apoptosis of activated T cells. Unlike normal liver, which appears to selectively remove only activated CD8+ T cells, enhanced apoptosis was seen for both CD4+ and CD8+ T cells. Enhanced apoptosis of activated T lymphocytes was associated with upregulation of FasL by HCV transgenic hepatocytes and was specifically inhibited by anti-FasL blocking antibody. Increased apoptosis of activated T cells induced by HCV structural proteins could amplify the ability of the liver to down-modulate T cell responses, leading to attenuation of anti-viral responses and facilitating viral persistence.
丙型肝炎病毒（HCV）感染中一个尚未解决的核心问题是该病毒如何建立慢性感染。最近的研究表明，肝脏微环境会导致活化T细胞凋亡，这可能与对肝移植的耐受性有关。在此，我们报告表达编码HCV结构蛋白核心、包膜1（E1）和包膜2（E2）的转基因的小鼠肝细胞会增强活化T细胞的凋亡。与正常肝脏似乎仅选择性清除活化的CD8 + T细胞不同，CD4 +和CD8 + T细胞均出现凋亡增强。活化T淋巴细胞凋亡增强与HCV转基因肝细胞FasL上调有关，并被抗FasL阻断抗体特异性抑制。HCV结构蛋白诱导的活化T细胞凋亡增加可增强肝脏下调T细胞反应的能力，导致抗病毒反应减弱并促进病毒持续存在。
