| [ISVHLD2012]针对病毒性肝炎的天然免疫和获得性免疫——Prof.Robert Thimme专访 -----
来源： 作者：R.Thimme 发布时间：2012-7-17 14:10:44 阅读：18
我的报告主要涉及这两种病毒，然而我将更关注于病毒感染导致的适应性免疫应答超过固有免疫应答。通过这方面研究我试图解释控制这些病毒感染患者适应性免疫应答失败而导致慢性乙肝和丙肝感染的主要原因。
Hepatology Digest: Regarding your presentation on immune responses towards viral hepatitis， will you focus predominantly on either HBV or HCV or both together?
《国际肝病》：您在报告中关注了病毒性肝炎免疫应答，您的研究是主要关注于乙型肝炎病毒还是丙型肝炎病毒还是两者兼关注？
Prof Robert Thimme: My presentation will cover both viruses; however I will focus more towards the adaptive immune response against them rather than the innate arm. From this I will attempt to explain the failure of the adaptive immune response in controlling these viruses in patients， which will in turn lead to chronic hepatitis B and C viral infection. The reasons for this I will highlight include the failure of viral T-cells and the emergence of viral escape mutations. In addition briefly I will also touch upon the innate immune response which is also very important in determining what type of adaptive response will be initiated against the virus. Interestingly at least in the case for HBV， the innate immune response does not appear to be induced. As a result of this some people refer to HBV as a stealth virus. On the other hand HCV can induce the innate immune system in a number of ways and I will also explain what we think are the measures HCV counters this response.
Prof Robert Thimme:我的报告主要涉及这两种病毒，然而我将更关注于病毒感染导致的适应性免疫应答超过固有免疫应答。通过这方面研究我试图解释控制这些病毒感染患者适应性免疫应答失败而导致慢性乙肝和丙肝感染的主要原因。我关注这方面的主要原因包括病毒T细胞的失败和病毒突变的出现。此外我仍将继续关注固有免疫，因为固有免疫可以决定抗病毒适应性免疫应答是哪种类型。有趣的是至少在HBV感染中固有免疫没有表现出被诱导出来，所以一些人认为HBV是一种潜在的病毒。而另一方面丙肝病毒可以通过很多方式诱导的固有免疫系统应答，因此我将试图解释我们所认为的HCV作用于固有免疫应答的方式。
Hepatology Digest: There have been suggestions that HBV has the capacity to suppress the immune response as opposed to evading it， what are your opinions regarding this?
《国际肝病》：有一些观点认为HBV通过抑制免疫应答方式而不是侵入免疫系统，您对此有什么观点？
Prof Robert Thimme; There has also been suggestions that there might be some interference with the innate immune response. However， especially in the chimpanzee model were experimental data has suggested that the innate response is not strongly induced during the early stages of infection. This is in stark contrast to HCV which has been shown to induce a rapid innate response during the early stages of infection. At this point I would say the answer is still open but it is safe to say that the innate immune response is not strongly induced with HBV infection.
Prof Robert Thimme:有一些观点认为可能有一些干扰因素影响了固有免疫应答。然而，特别在猩猩动物模型中的实验数据认为在HBV感染早期没有诱导出固有免疫应答。而HCV感染完全相反的是在感染早期可以诱导快速固有免疫应答。在这一点结果我认为还是仍然需要证实，但可以肯定的是在HBV感染中没有诱导出很强的固有免疫。
Hepatology Digest: You mentioned that the reason why HBV and HCV lead chronic liver disease is attributed to the failure of the adaptive immune response?
《国际肝病》：您提到了HBV和HCV感染导致的慢性肝脏疾病的原因是由于适应性免疫应答的失败对么？
Prof Robert Thimme; I think both arms of the immune response are important. The failure of the early innate response to be induced which has a knock on effect towards the adaptive response to be initiated to control the virus. It is very clear that spontaneous HBV and HCV clearance is associated with a robust and more importantly specific adaptive CD4 and CD8 T-cell immune responses. If there is a defect in these T-cells， if the cells are not totally functional or if the virus has the capacity to escape these cells， then viral persistence will occur.
Prof Robert Thimme:我认为所有的免疫应答（包括固有免疫和适应性免疫应答）都很重要。早期固有免疫应答的失败影响了适应性免疫应答开始控制病毒的效果。非常肯定的是自发性HBV和HCV清除与强烈和非常重要的特异性CD4+T和CD8+T细胞免疫应答有关。假如这些T细胞存在缺陷，假如这些细胞功能缺失或者假如病毒有逃避这些细胞作用的能力，将出现病毒的持续感染。
Hepatology Digest: There has been talk about how the body controls the body’s immune response in order to avoid liver injury. Is it possible that in some cases that the failure to clear the virus is due to the functional inhibition of the acquired immunity?
《国际肝病》：有研究关注宿主如何控制宿主免疫应答来避免肝脏损伤。这种控制可能在某些情况下由于获得性免疫功能的抑制造成清除病毒失败？
Prof Robert Thimme: That is absolutely true， and there has been recent data showing that T- regulatory cells are suppressing the immune response in order to avoid tissue damage. It has also been suggested that immune suppressing cytokines such as IL-10 and additionally the up-regulation of inhibitory receptors on the surface of the HBV specific CD-8- T- cells may also play a role in this setting. However， these factors in preventing the severity of tissue damage may also contribute towards viral persistence.
Prof Robert Thimme:这种观点完全正确的，最近的研究数据说明了调节性T细胞抑制免疫应答为了避免组织损伤。也有认为免疫抑制细胞因子如IL-10以及HBV特异性CD8+T细胞表面抑制性受体表达上调在这种状态下起了重要作用。然而这些因素是为了防止组织损伤的加重同时也是病毒持续存在的原因。
Hepatology Digest: Would you say that these are major factors towards viral persistence?
《国际肝病》：您是否认为这些是导致病毒持续存在的主要因素？
Prof Robert Thimme: We cannot give a concrete answer and I think the relative contributions of all of these factors need to be studied in more detail. Perhaps， in the future these different areas might provide interesting targets for immune-therapy.
Prof Robert Thimme:我们不能给出具体的答案并且我认为所有相关的这些因素的作用需要更加详细的研究。或许，在将来这些不同领域的研究结果可以提供有意义的免疫治疗的靶点。
Hepatology Digest: Regarding immune therapies for viral hepatitis， we already have interferon and some genetic and T cell implantation studies which hold promise for the future. In your view what do you think will be the most interesting prospective development in the near future?
《国际肝病》：谈到对于病毒性肝炎的免疫治疗，我们已经有了干扰素和一些基因以及T细胞移植研究并且在将来很有前景。在您的观点中您认为哪些在不久的将来发展中更加有前景呢？
Prof Robert Thimme: In order to go forward with the best experimental approach we must first understand more clearly the mechanisms which contribute to the failure of the adaptive immune responses. I think with the induction of the immune response as previously achieved with the adenovirus may also be applied to HCV infection. This may provide promising therapeutic potential as well as the depletion of regulatory T cells together with the up regulation of viral specific cytokines. These measures can influence the recruitment of lymphocytes to the liver， but need to be studied in more detail to determine which approach will be most effective.
Prof Robert Thimme:为了通过最佳实验方法深入研究，我们必须首先清楚地了解导致获得性免疫应答失败的原因。我认为诱导免疫应答在过去通过腺病毒应用在HCV感染中可以获得。这为去除调节性T细胞同时上调病毒特异性细胞因子提供了潜在的治疗价值。这些手段可影响淋巴细胞的募集到肝脏，但是需要进行更多细化的研究来决定哪一种方法是最有效的。
Hepatology Digest: There have been suggestions that one of the main reasons of viral chronic liver damage is due to a weak viral specific T cell response being sub-optimal in clearing the virus. From this cells of the innate response such as the macrophages will cause damage to the organ， would it therefore be more dangerous encouraging cells other than the T-cells towards the liver?
《国际肝病》：有些观点认为慢性病毒引起的肝损伤主要原因之一是由于病毒特异性T细胞应答减弱造成清除病毒能力下降。通过这些固有免疫应答的细胞如巨噬细胞可造成器官的损伤，因此可能增加更多造成对肝脏有损伤的细胞而不是T细胞？
Prof Robert Thimme: Indeed there is a large fraction of non HBV specific inflammation， which contributes to ongoing liver disease. This has been shown especially for HBV， and in my opinion immune therapy should be focused on antigen specific immune responses.
Prof Robert Thimme:实际上有一大部分是由HBV导致的非特异性炎症，造成了肝脏疾病的进展。这需要说明的是特别是对于HBV感染，在我的观点中免疫治疗应该更加关注在抗原特异性的免疫应答。
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发表于 2012-7-18 11:25
