文章导读：丙型肝炎患者存在两种不同的人群，一种共表达抑制性受体，另一种不表达。表达抑制性受体的患者能够识别抗原，不表达受体的患者不能识别抗原，出现病毒逃逸。因此，存在两种不同的病毒T细胞失败机制，分别反映发生了病毒逃逸还是T细胞功能缺陷。
Hepatology Digest: You mentioned that there distinct differences of CD8 T cells in HCV patients . Can you please elaborate on this?
《国际肝病》：您曾提到，丙型肝炎患者之间的CD8+T细胞存在明显区别。您能详细解释一下吗？
Prof Robert Thimme: For HCV patients we have two distinct populations which are either co expressing the inhibitor receptor or not. And the ones which are expressing the inhibitory receptor are recognizing antigens， the ones which do not express this do not because viral escape has occurred. As a result we have 2 different mechanisms of viral T cell failure reflecting on whether viral escape or T cell dysfunction has occurred.
Thimme教授：丙型肝炎患者存在两种不同的人群，一种共表达抑制性受体，另一种不表达。表达抑制性受体的患者能够识别抗原，不表达受体的患者不能识别抗原，出现病毒逃逸。因此，存在两种不同的病毒T细胞失败机制，分别反映发生了病毒逃逸还是T细胞功能缺陷。
Hepatology Digest: Are there any specific therapeutic avenues targetting this?
《国际肝病》：针对这种现象，有特异的治疗途径吗？
Prof Robert Thimme: I thi nk we have to focus on the inhibitory receptors， in order to ensure that the CD8 T cells are functioning again. However， this is difficult because as we have shown even with the addition of cytokines for three days in mouse models is still not enough. I think siRNAs could be a useful tool if you can make it work in animal models to reverse the inhibitory dysfunction of the T-cells.
Thimme教授：我认为，我们必须将重点放在抑制性受体上，以确保CD8+T细胞能再次应答。但是这很困难，因为我们已经在小鼠模型上观察到即便应用3天细胞因子，仍然不够。我想，如果我们能在动物模型上用siRNA成功逆转T细胞抑制性功能障碍，它应该是一个有用的工具。
Hepatology Digest: In terms of CD4 cell profiles， what are the main differences between HBV and HCV patients.
《国际肝病》：关于CD4+T细胞特征，乙型肝炎和丙型肝炎患者之间主要的差别是什么？
Prof Robert Thimme: We have not studied this in detail， but there has been a study in Gastroenterology that HBV patients they also express inhibitory receptors just like in HCV patients. The consensus finding is that CD4 T cells seem to be completely dysfunctional in chronic infected patients.
Robert Thimme教授：我们没有详细研究这个。但是Gastroenterology杂志上有一项研究，乙型肝炎患者和丙型肝炎患者一样也表达抑制性受体。与之一致的发现是，慢性感染者的CD4+T细胞好像功能完全缺陷。
Hepatology Digest: Do you think this can be related to IL-28?
《国际肝病》：您认为这和IL-28有关吗？
Prof Robert Thimme: I do not think IL-28 polymorphisms correlates with T cell responses. We looked at that ourselves and we did not find any relation.
Robert Thimme教授：我不认为IL-28多态性与T细胞反应有关。我们自己的研究没有发现任何相关性。
Hepatology Digest: Where does the future research directive hold in this area?
《国际肝病》：这个领域将来的研究指向哪里？
Prof Robert Thimme: I think it is very important to understand the mechanisms of T-cell failure better in order for us to develop more immune therapies. This is because we still do not know the relative contributions of all the pathways and their roles in T-cell failure， the role of viral escape， and the determinants of T-cell failure. All these have to studied in more detail in order for us to develop better immuno-therapy choices.
Robert Thimme教授：更好地理解T细胞障碍的机制非常重要。这是因为我们仍然不知道所有途径的相对贡献及它们在T细胞障碍中的作用、在病毒逃逸中的作用及T细胞障碍的决定因素。必须对所有这些问题详细研究，以发现更好的免疫治疗方法。
Hepatology Digest: You mentioned that there distinct differences of CD8 T cells in HCV patients . Can you please elaborate on this?
《国际肝病》：您曾提到，丙型肝炎患者之间的CD8+T细胞存在明显区别。您能详细解释一下吗？
Prof Robert Thimme: For HCV patients we have two distinct populations which are either co expressing the inhibitor receptor or not. And the ones which are expressing the inhibitory receptor are recognizing antigens， the ones which do not express this do not because viral escape has occurred. As a result we have 2 different mechanisms of viral T cell failure reflecting on whether viral escape or T cell dysfunction has occurred.
Thimme教授：丙型肝炎患者存在两种不同的人群，一种共表达抑制性受体，另一种不表达。表达抑制性受体的患者能够识别抗原，不表达受体的患者不能识别抗原，出现病毒逃逸。因此，存在两种不同的病毒T细胞失败机制，分别反映发生了病毒逃逸还是T细胞功能缺陷。
Hepatology Digest: Are there any specific therapeutic avenues targetting this?
《国际肝病》：针对这种现象，有特异的治疗途径吗？
Prof Robert Thimme: I thi nk we have to focus on the inhibitory receptors， in order to ensure that the CD8 T cells are functioning again. However， this is difficult because as we have shown even with the addition of cytokines for three days in mouse models is still not enough. I think siRNAs could be a useful tool if you can make it work in animal models to reverse the inhibitory dysfunction of the T-cells.
Thimme教授：我认为，我们必须将重点放在抑制性受体上，以确保CD8+T细胞能再次应答。但是这很困难，因为我们已经在小鼠模型上观察到即便应用3天细胞因子，仍然不够。我想，如果我们能在动物模型上用siRNA成功逆转T细胞抑制性功能障碍，它应该是一个有用的工具。
Hepatology Digest: In terms of CD4 cell profiles， what are the main differences between HBV and HCV patients.
《国际肝病》：关于CD4+T细胞特征，乙型肝炎和丙型肝炎患者之间主要的差别是什么？
Prof Robert Thimme: We have not studied this in detail， but there has been a study in Gastroenterology that HBV patients they also express inhibitory receptors just like in HCV patients. The consensus finding is that CD4 T cells seem to be completely dysfunctional in chronic infected patients.
Robert Thimme教授：我们没有详细研究这个。但是Gastroenterology杂志上有一项研究，乙型肝炎患者和丙型肝炎患者一样也表达抑制性受体。与之一致的发现是，慢性感染者的CD4+T细胞好像功能完全缺陷。
Hepatology Digest: Do you think this can be related to IL-28?
《国际肝病》：您认为这和IL-28有关吗？
Prof Robert Thimme: I do not think IL-28 polymorphisms correlates with T cell responses. We looked at that ourselves and we did not find any relation.
Robert Thimme教授：我不认为IL-28多态性与T细胞反应有关。我们自己的研究没有发现任何相关性。
Hepatology Digest: Where does the future research directive hold in this area?
《国际肝病》：这个领域将来的研究指向哪里？
Prof Robert Thimme: I think it is very important to understand the mechanisms of T-cell failure better in order for us to develop more immune therapies. This is because we still do not know the relative contributions of all the pathways and their roles in T-cell failure， the role of viral escape， and the determinants of T-cell failure. All these have to studied in more detail in order for us to develop better immuno-therapy choices.
Robert Thimme教授：更好地理解T细胞障碍的机制非常重要。这是因为我们仍然不知道所有途径的相对贡献及它们在T细胞障碍中的作用、在病毒逃逸中的作用及T细胞障碍的决定因素。必须对所有这些问题详细研究，以发现更好的免疫治疗方法。
