Magnitude of CD8+ T-cell responses against hepatitis C virus and severity of hepatitis do not necessarily determine outcomes in acute hepatitis C virus infection
Magnitude of CD8+ T-cell responses against hepatitis C virus and severity of hepatitis do not necessarily determine outcomes in acute hepatitis C virus infection
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DOI：
10.1111/j.1872-034x.2008.00459.x
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发表时间：
2009-03-01
影响因子：
4.2
通讯作者：
Imawari, Michio
中科院分区：
文献类型：
--
作者：
Doi, Hiroyoshi;Hiroishi, Kazumasa;Imawari, Michio
我们研究了丙型肝炎病毒（HCV）特异性CD 8（+）T细胞反应的程度与急性HCV感染临床病程之间的关系。HCV特异性CD 8（+）T细胞应答的分析使用基于干扰素-γ的酶联免疫斑点试验，使用外周CD 8（+）T细胞、单核细胞和297个20-mer合成肽，其重叠10个残基并跨越基因型1b的整个HCV序列。5名患者针对单一和不同的肽表现出可检测的HCV特异性CD 8（+）T细胞应答，而1名患者显示出对三种不同肽的应答。HCV特异性CD 8（+）T细胞应答的大小和肝炎的严重程度都不能预测急性肝炎的结局。6例急性HCV感染患者均检测到HCV特异性CD 8（+）T细胞应答，并鉴定出6个新的HCV特异性CTL表位。急性HCV感染可以通过可检测到的HCV特异性CD 8（+）T细胞应答而消退，但不会产生抗HCV抗体。
We investigated the relationship between the magnitude of comprehensive hepatitis C virus (HCV)-specific CD8(+) T-cell responses and the clinical course of acute HCV infection.Six consecutive patients with acute HCV infection were studied. Analysis of HCV-specific CD8(+) T-cell responses was performed using an interferon-gamma-based enzyme-linked immunospot assay using peripheral CD8(+) T-cells, monocytes and 297 20-mer synthetic peptides overlapping by 10 residues and spanning the entire HCV sequence of genotype 1b.Five patients presented detectable HCV-specific CD8(+) T-cell responses against a single and different peptide, whereas 1 patient showed responses against three different peptides. Neither the magnitude of HCV-specific CD8(+) T-cell responses nor the severity of hepatitis predicts the outcome of acute hepatitis. The maximum number of HCV-specific CD8(+) T-cells correlated with maximum serum alanine aminotransferase level during the course (r = 0.841, P = 0.036).HCV-specific CD8(+) T-cell responses were detectable in all 6 patients with acute HCV infection, and 6 novel HCV-specific CTL epitopes were identified. Acute HCV infection can resolve with detectable HCV-specific CD8(+) T-cell responses, but without development of antibody against HCV.