Tracking Virus-Specific CD4+T Cells during and after Acute Hepatitis C Virus Infection
Tracking Virus-Specific CD4+T Cells during and after Acute Hepatitis C Virus Infection
复制标题
DOI：
10.1371/journal.pone.0000649
复制
发表时间：
2007-07-25
期刊：
影响因子：
3.7
通讯作者：
Diepolder, Helmut M.
中科院分区：
文献类型：
--
作者：
Lucas, Michaela;Ulsenheimer, Axel;Diepolder, Helmut M.
背景资料。CD4+T细胞帮助在维持抗病毒免疫反应方面至关重要，这种帮助已被证明在急性缓解丙型肝炎中持续存在。相比之下，使用功能分析，在演变的慢性丙型肝炎中，CD4+T细胞辅助反应似乎是缺失或短暂的。方法/主要调查结果。在这里，我们使用了一种含有丙型肝炎病毒非结构蛋白4的高靶向性CD4+T细胞表位的新型HLA-DR1四聚体，以跟踪与慢性丙型肝炎或缓解丙型肝炎患者相比的七名急性丙型肝炎患者中丙型肝炎病毒特异性CD4+T细胞的数量和表型。我们观察了所有七名急性丙型肝炎患者中的肽特异性T细胞，无论预后如何，CD4+T细胞的比例高达0.65%。在暂时控制病毒复制的患者中，我们观察到病毒复发前四聚体+CD4+T细胞功能丧失和/或物理缺失。在一些慢性丙型肝炎患者中，在外周血中检测到非常少量的四聚体+细胞，而在自发解决者中检测到强烈的反应。重要的是，在慢性丙型肝炎患者中，我们没有观察到这一关键的CD4+T细胞表位的逃逸突变。在急性丙型肝炎期间，针对该表位的CD4+T细胞反应很容易在大多数，如果不是全部的话，在HLA-DR1+患者中被诱导。在病毒血症持续存在的患者中，这种抗病毒T细胞群在病程早期变得功能受损或被删除。
Background. CD4+ T cell help is critical in maintaining antiviral immune responses and such help has been shown to be sustained in acute resolving hepatitis C. In contrast, in evolving chronic hepatitis C CD4+ T cell helper responses appear to be absent or short-lived, using functional assays. Methodology/Principal Findings. Here we used a novel HLA-DR1 tetramer containing a highly targeted CD4+ T cell epitope from the hepatitis C virus non-structural protein 4 to track number and phenotype of hepatitis C virus specific CD4+ T cells in a cohort of seven HLA-DR1 positive patients with acute hepatitis C in comparison to patients with chronic or resolved hepatitis C. We observed peptide-specific T cells in all seven patients with acute hepatitis C regardless of outcome at frequencies up to 0.65% of CD4+ T cells. Among patients who transiently controlled virus replication we observed loss of function, and/or physical deletion of tetramer+ CD4+ T cells before viral recrudescence. In some patients with chronic hepatitis C very low numbers of tetramer+ cells were detectable in peripheral blood, compared to robust responses detected in spontaneous resolvers. Importantly we did not observe escape mutations in this key CD4+ T cell epitope in patients with evolving chronic hepatitis C. Conclusions/Significance. During acute hepatitis C a CD4+ T cell response against this epitope is readily induced in most, if not all, HLA-DR1+ patients. This antiviral T cell population becomes functionally impaired or is deleted early in the course of disease in those where viremia persists.