【HBeAg阴性慢性乙型肝炎中的细胞免疫应答】

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published on Journal of Viral Hepatitis, March 2008
原载《病毒性肝炎》杂志，2008年三月刊

Cellular immune responses in hepatitis B virus e antigen negative chronic hepatitis B

KEYWORDS
acute hepatitis B • cellular immunity • chronic hepatitis B • hepatitis B surface antigen • hepatitis B virus • interferon γ

ABSTRACT
Summary. The immunopathogenesis of hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) virus (HBV) infection has not been adequately investigated. We studied the cellular immune responses of peripheral lymphocytes using proliferating assays, intracellular cytokine staining (ICS) and ELISPOT interferon-γ (IFN-γ) assays after non-specific and specific stimulation with whole HBV proteins and synthetic peptides. Thirty patients with HBeAg negative CHB, eleven HBsAg inactive carriers, nine patients with acute hepatitis B and 22 healthy controls were included in the study. Patients with HBeAg negative CHB demonstrated an increased number of peripheral CD8+ T cells while their peripheral blood mononuclear cells showed increased proliferation after in vitro stimulation with overlapping hepatitis B core derived peptides and an envelope derived epitope (HBs 182–191 aa), similar to those observed in acute hepatitis B. Using ICS, we found an expanded population of IFN-γ producing T lymphocytes, CD4+ and CD8+, after non-specific stimulation, in HBeAg negative CHB compared to all other groups. HBeAg negative CHB and acute hepatitis B patients had a similarly increased number of core specific T cells measured by the IFN-γ assays. Inactive HBsAg carriers showed minimal proliferative responses overall while they exhibited an increased number of envelope specific effector T cells (measured by ICS). In conclusion, we showed that overall CD4+ T cell responses from patients with HBeAg negative CHB were comparable to those of acute hepatitis B, while inactive HBsAg carriers despite their limited proliferative capacity the effector activity of their peripheral T cells was maintained.

Received February 2008; accepted for publication March 2008

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全文

战战兢兢

多谢，下载了，但English有限，读确实有困难。

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可以只看结论部分：

Collectively, these results show that in patients with HBeAg negative CHB peripheral T cells (mainly CD4+) exhibit proiferative capacity against a number of antigenic epitopes from the core and envelope proteins. Furthermore, despite the fact that the total number of peripheral effector T cells was expanded, the number of specific cells against the core and envelope proteins was relatively low (<1%). This could indicate an activation of non-specific T cells during hepatitis flares responsible for the liver necroinflammation observed in these patients.

综合的说，上述研究结果显示HBeAg阴性的乙肝患者的外周T细胞（主要是CD4+）对病毒的核心蛋白和鞘蛋白表现出增生能力。但是，虽然外周效应T细胞的总数量扩大了，但是针对于核心蛋白和鞘蛋白的特异细胞的数量仍然有限（小于1%）。这可能提示，非特异性T细胞的启动是“肝脏发炎”期间造成肝脏坏死炎症的直接因素。

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Patients with acute hepatitis B demonstrated proliferative responses similar to those seen in HBeAg negative CHB. In contrast to CHB patients though, the total pool of effector T cells was not expanded. Nevertheless, IFN-gama assays showed a relatively increased number of HBcAg and HBsAg specific effector T cells within this population. This could imply that during the course of acute Hepatitis B, a more focused and efficient specific cellular immune response is delivered that is capable of achieving viral clearance.

急性乙肝病人虽然也和HBeAg阴性的慢性乙肝患者一样表现出类似的增生（扩散）应答，但是效应T细胞的总数没有明显扩张。而伽玛干扰素分析显示针对 HBcAg和HBsAg的特异性T细胞的数量相对增加了。这可能提示在急性乙肝患者免疫系统的细胞应答更有针对性也更有效，从而可能将病毒清除。

（译者按：请换个思路老师留意，文章这里从免疫病理学的角度回答了为什么有的人能够完全清除病毒--特异性T细胞的增加，而慢性乙肝患者的细胞应答缺乏足够的特异性）

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Patients with chronically inactive liver disease (HBsAg inactive carriers) showed minimal proliferative capacity against HBc and HBc-derived peptides, while they retained a relatively increased pool of effector T cells. Within this population, an expanded subset of envelope specific cells was present. Maini et al. [26] have recently shown using MHC-Itetramers, that HBsAg inactive carriers, maintain a number of functional CD8+ T lymphocytes in the hepatic parenchyma and the periphery. Although, in our study the functional characteristics of these T cells was not investigated, we can speculate that in HBsAg inactive carriers, a dynamic population of HBV specific T cells, both in the liver and periphery exists, that is able to produce antiviral cytokines (i.e. IFN-gama) and thus suppress HBV replication without cytolytic liver damage.

对于慢性非活动性乙肝（HBsAg阳性的携带者），免疫系统针对HBc（乙肝病毒核心蛋白）和源自HBc的缩氨酸的增生能力最低，但是效应T细胞池相对比较大。在这个效应T细胞池中，有针对病毒鞘蛋白的特异细胞存在。Maini在《病毒特异性CD8+细胞在持续性乙肝感染导致的肝损伤和病毒控制中的角色》中认为在非活动性乙肝患者的肝组织和外周中保有一定数量的CD8+ T淋巴细胞。我们虽然没有研究这些细胞的功能特征，但是可以推测：非活动性乙肝病人机体内，有一个具有动态数量的HBV特异性T细胞群，在肝组织和外周都存在，它们能够产生抗病毒因子（比如伽玛干扰素）抑制病毒的复制，同时不造成肝细胞损伤。

小小刘

好文章，大家赶快了解一下吧。