Differential CD4+ and CD8+ T-cell responsiveness in hepatitis C virus infection
Differential CD4+ and CD8+ T-cell responsiveness in hepatitis C virus infection
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DOI：
10.1053/jhep.2001.21162
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发表时间：
2001-01-01
期刊：
影响因子：
13.5
通讯作者：
Chisari, FV
中科院分区：
文献类型：
--
作者：
Chang, KM;Thimme, R;Chisari, FV
本研究旨在比较丙型肝炎病毒感染后不同病毒学和临床转归患者的病毒特异性CD4(+)和CD8(+)T细胞应答的活力和表型。结果表明，在丙型肝炎病毒感染恢复后，强健的、多特异性的CD4(+)增殖性T细胞反应被无限期地维持，而在持续感染的患者中，这种反应很弱且集中。相反，尽管使用了灵敏的体外直接细胞内干扰素-γ染色，但两组患者的丙型肝炎病毒特异性CD8(+)T细胞反应在数量上都很低。此外，尽管在体外无法检测到丙型肝炎病毒特异的细胞溶解CD8(+)记忆T细胞，但它们很容易从慢性丙型肝炎患者的外周血中扩增，但在体外刺激后不能从恢复的受试者中扩增，这表明持续的病毒血症是维持丙型肝炎特异记忆CD8(+)T细胞反应所必需的，丙型肝炎病毒特异的CD8(+)T细胞表现出I型细胞因子谱，其特征是尽管持续的丙型肝炎病毒血症，但仍产生干扰素-γ。在病毒清除后，丙型肝炎病毒特异性的CD4(+)T细胞存活，而CD8(+)T细胞丢失，这一矛盾的观察表明，在丙型肝炎病毒感染期间，对维持CD4(+)和CD8(+)T细胞的记忆存在不同的要求。此外，慢性感染患者循环中CD8(+)效应T细胞的相对稀少可能解释了肝脏炎症的慢性潜伏性本质，也解释了为什么它们无法清除病毒。
This study was performed to compare the vigor and phenotype of virus-specific CD4(+) and CD8(+) T-cell responses in patients with different virologic and clinical outcomes after hepatitis C virus (HCV) infection. The results show that a vigorous and multispecific CD4(+) proliferative T-cell response is maintained indefinitely after recovery from HCV infection whereas it is weak and focused in persistently infected patients. In contrast, the HCV-specific CD8(+) T-cell response was quantitatively low in both groups despite the use of sensitive direct ex vivo intracellular interferon gamma (IFN-gamma) staining. Furthermore, although HCV-specific cytolytic CD8(+) memory T cells were undetectable ex vivo, they were readily expanded from the peripheral blood of chronically HCV-infected patients but not from recovered subjects after in vitro stimulation, suggesting that ongoing viremia is required to maintain the HCV-specific memory CD8(+) T-cell response, HCV-specific CD8(+) T cells displayed a type I cytokine profile characterized by production of IFN-gamma despite persistent HCV viremia. The paradoxical observation that HCV-specific CD4(+) T cells survive and CD8(+) T cells are lost after viral clearance while the opposite occurs when HCV persists suggests the existence of differential requirements for the maintenance of CD4(+) and CD8(+) T-cell memory during HCV infection. Furthermore, the relative rarity of circulating CD8(+) effector T cells in chronically infected patients may explain the chronic insidious nature of the liver inflammation and also why they fail to eliminate the virus.