Sustained dysfunction of antiviral CD8+ T lymphocytes after infection with hepatitis C virus
Sustained dysfunction of antiviral CD8+ T lymphocytes after infection with hepatitis C virus
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DOI：
10.1128/jvi.75.12.5550-5558.2001
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发表时间：
2001-06-01
影响因子：
5.4
通讯作者：
Klenerman, P
中科院分区：
文献类型：
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作者：
Gruener, NH;Lechner, F;Klenerman, P
丙型肝炎病毒（HCV）在大多数暴露者中造成持续感染。与其他持续性病毒感染一样，t淋巴细胞反应的效果可能影响长期结果。然而，对于急性感染后诱导的hcv特异性t淋巴细胞反应的功能能力知之甚少。我们通过使用主要的组织相容性复合体i类肽四聚体复合体（四聚体）来研究这一点，它可以独立于功能直接检测特异性CD8(+) T淋巴细胞。在这里，我们表明，感染后早期，用四种这样的四聚体检测到的病毒特异性CD8(+) T淋巴细胞在抗病毒细胞因子的合成和裂解活性方面异常。此外，这种表型通常是长期维持的，因为在体外测量中发现了大量持续的hcv特异性CD8+ T淋巴细胞，其抗病毒细胞因子反应一直很差。总的来说，与eb病毒和/或巨细胞病毒相比，hcv特异性CD8(+) T淋巴细胞在有丝分裂原或肽刺激后，肿瘤坏死因子α (tnf - α)和γ干扰素（ifn - γ）的合成减少。HCV感染后诱导的抗病毒CD8(+) T淋巴细胞的这种行为可能通过未能有效抑制病毒复制而导致病毒持续存在。
Hepatitis C virus (HCV) sets up persistent infection in the majority of those exposed. It is likely that, as with other persistent viral infections, the efficacy of T-lymphocyte responses influences long-term outcome. However, little is known about the functional capacity of HCV-specific T-lymphocyte responses induced after acute infection. We investigated this by using major histocompatibility complex class I-peptide tetrameric complexes (tetramers), which allow direct detection of specific CD8(+) T lymphocytes ex vivo, independently of function. Here we show that, early after infection, virus-specific CD8(+) T lymphocytes detected with a panel of four such tetramers are abnormal in terms of their synthesis of antiviral cytokines and lytic activity. Furthermore, this phenotype is commonly maintained long term, since large sustained populations of HCV-specific CD8+ T Lymphocytes were identified, which consistently had very poor antiviral cytokine responses as measured in vitro. Overall, HCV-specific CD8(+) T lymphocytes show reduced synthesis of tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma) after stimulation with either mitogens or peptides, compared to responses to Epstein-Barr virus and/or cytomegalovirus. This behavior of antiviral CD8(+) T lymphocytes induced after HCV infection may contribute to viral persistence through failure to effectively suppress viral replication.