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回复 newchinabok 的帖子
"陈新月教授分析是cd8耗竭，要停一下再打" - 这是陈新月教授个人的看法 .
从他的参考文献中 , Dissecting the divergent effects of interferon-alpha on immune cells: Time to rethink combination therapy in chronic hepatitis B?
Robert Thimme
Maura Dandri
剖析干扰素-α对免疫细胞的不同作用：是时候重新考虑慢性乙型肝炎的联合治疗了吗？
罗伯特·蒂姆（Robert Thimme）
莫拉·丹德里（Maura Dandri）
https://www.journal-of-hepatolog ... 12)00871-9/fulltext
"Indeed, PegIFNα therapy led to a striking reduction of CD8+ T cells, an effect that was most pronounced on predominantly end-stage effector cells compared to naïve and central memory subsets. Even more importantly, HBV-specific CD8+ T cells remained at low frequency and no restoration of their effector functions was observed. In line with this finding, the expression levels of inhibitory markers, such as PD-1 or CTLA-4, were not affected by IFN-α therapy. These results are in agreement with previous studies that have analyzed the immunomodulatory effects of IFN-α on T cells. For example, Penna et al. have recently reported that PegIFNα does not improve early peripheral blood HBV-specific T cell responses in HBeAg negative chronic hepatitis [[31]
]. Most likely, IFN-α suppresses T cell responses by its strong antiproliferative effect. However, it is also possible that indirect effects, such an NK cell mediated inhibition of T cells, may contribute to the IFN mediated inhibition of T-cell responses. Whatever the explanation, the elegant results obtained by Micco et al. clearly demonstrate a differential boosting of innate and adaptive antiviral immune responses during PegIFNα treatment [[22]
], whereby hinting at the limited capacities of this treatment regimen to restore, at least on short term, HBV-specifc T-cell functions."
确实，PegIFNα治疗导致CD8 + T细胞显着减少，与幼稚和中枢记忆子集相比，这种作用在主要是末期效应细胞上最为明显。更为重要的是，HBV特异性CD8 + T细胞仍处于低频状态，并且未观察到其效应子功能的恢复。与该发现一致，IFN-α疗法不抑制抑制标志物如PD-1或CTLA-4的表达水平。这些结果与以前的研究一致，后者分析了IFN-α对T细胞的免疫调节作用。例如，Penna等。最近报道，在HBeAg阴性慢性肝炎中，PegIFNα不能改善早期外周血HBV特异性T细胞反应[[31]
]。 IFN-α最有可能通过其强大的抗增殖作用抑制T细胞应答。但是，间接作用（例如NK细胞介导的T细胞抑制）也可能有助于IFN介导的T细胞应答抑制。不论作出何种解释，Micco等人都能获得优美的结果。清楚地证明了PegIFNα治疗期间先天性和适应性抗病毒免疫应答的差异性增强[[22]
]，这暗示了该治疗方案至少在短期内恢复了HBV特异性T细胞功能的能力有限。
停止干扰素可以增加HBV特异性T细胞的数量吗？ |
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楼主: lhwwjx
发表于 2021-3-27 08:22
