Full-breadth analysis of CD8+ T-cell responses in acute hepatitis C virus infection and early therapy
Full-breadth analysis of CD8+ T-cell responses in acute hepatitis C virus infection and early therapy
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DOI：
10.1128/jvi.79.20.12979-12988.2005
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发表时间：
2005-10-01
影响因子：
5.4
通讯作者：
Walker, BD
中科院分区：
文献类型：
--
作者：
Lauer, GM;Lucas, M;Walker, BD
多特异性CD8（+）T细胞应答被认为对控制急性丙型肝炎病毒（KCV）感染很重要，但迄今为止，关于早期时间点应答广度的实际信息很少。此外，早期治疗对这些反应的影响及其与结果的关系是有争议的。为了研究这个问题，我们在8名急性感染者中对病毒特异性CD8（+）T细胞应答的广度和频率进行了全面分析，这些人都开始了早期治疗。在急性期，对多达五个肽的反应进行了鉴定。在治疗过程中，随着病毒的控制，CD8（+）T细胞反应降低而不是增加，并且没有出现新的特异性。治疗完成后的持续病毒学应答与CD8（+）T细胞应答以及CD4（+）T细胞应答无关。尽管有广泛的CD8（+）T细胞应答，但也会发生快速复发。重要的是，在一名受试者中使用OKT 3体内抑制CD3（+）T细胞并没有导致病毒血症复发。这些数据表明，单靠广泛的CD8（+）T细胞应答可能不足以遏制HCV复制，而且早期治疗是有效的，与这些应答无关。
Multispecific CD8(+) T-cell responses are thought to be important for the control of acute hepatitis C virus (KCV) infection, but to date little information is actually available on the breadth of responses at early time points. Additionally, the influence of early therapy on these responses and their relationships to outcome are controversial. To investigate this issue, we performed comprehensive analysis of the breadth and frequencies of virus-specific CD8(+) T-cell responses on the single epitope level in eight acutely infected individuals who were all started on early therapy. During the acute phase, responses against up to five peptides were identified. During therapy, CD8(+) T-cell responses decreased rather than increased as virus was controlled, and no new specificities emerged. A sustained virological response following completion of treatment was independent of CD8(+) T-cell responses, as well as CD4(+) T-cell responses. Rapid recrudescence also occurred despite broad CD8(+) T-cell responses. Importantly, in vivo suppression of CD3(+) T cells using OKT3 in one subject did not result in recurrence of viremia. These data suggest that broad CD8(+) T-cell responses alone may be insufficient to contain HCV replication, and also that early therapy is effective independent of such responses.