Liver-infiltrating lymphocytes in chronic human hepatitis C virus infection display an exhausted phenotype with high levels of PD-1 and low levels of CD127 expression
Liver-infiltrating lymphocytes in chronic human hepatitis C virus infection display an exhausted phenotype with high levels of PD-1 and low levels of CD127 expression
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DOI：
10.1128/jvi.02021-06
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发表时间：
2007-03-01
影响因子：
5.4
通讯作者：
Grakoui, Arash
中科院分区：
文献类型：
--
作者：
Radziewicz, Henry;Ibegbu, Chris C.;Grakoui, Arash
大多数丙型肝炎病毒(丙型肝炎病毒)感染者无法产生或维持有效的T细胞反应来清除病毒。来自小鼠慢性病毒感染的证据表明，共抑制分子PD-1的表达预示着CD8(+)抗病毒T细胞的耗竭，并可能导致病原体控制不足。为了研究人CD8+T细胞在慢性丙型肝炎病毒感染过程中是否表达PD-1并表现出功能紊乱的表型，我们检测了外周血和肝内特异的CD8(+)T细胞。我们发现，在慢性丙型肝炎病毒感染中，外周血中丙型肝炎病毒特异性T细胞表达高水平的PD-1，阻断PD-1/PD-L1相互作用导致增殖能力增强。重要的是，与外周相比，肝内丙型肝炎病毒特异性T细胞不仅表达高水平的PD-1，而且还降低白介素7受体α(CD127)，这是一种耗尽的表型，是丙型肝炎病毒抗原特异的，并被分割到肝脏，病毒复制的地点。
The majority of people infected with hepatitis C virus (HCV) fail to generate or maintain a T-cell response effective for viral clearance. Evidence from murine chronic viral infections shows that expression of the coinhibitory molecule PD-1 predicts CD8(+) antiviral T-cell exhaustion and may contribute to inadequate pathogen control. To investigate whether human CD8+ T cells express PD-1 and demonstrate a dysfunctional phenotype during chronic HCV infection, peripheral and intrahepatic HCV-specific CD8(+) T cells were examined. We found that in chronic HCV infection, peripheral HCV-specific T cells express high levels of PD-1 and that blockade of the PD-1/PD-L1 interaction led to an enhanced proliferative capacity. Importantly, intrahepatic HCV-specific T cells, in contrast to those in the periphery, express not only high levels of PD-1 but also decreased interleukin-7 receptor alpha (CD127), an exhausted phenotype that was HCV antigen specific and compartmentalized to the liver, the site of viral replication.