慢性HBV感染和纤维化患者特异性针对凋亡相关表位的CD8 + T细

StephenW

CD8+ T cells specific to apoptosis‐associated epitopes are expanded in patients with chronic HBV infection and fibrosis
Ilenia Pacella
Ilenia Cammarata
Carmela Martire
Giuseppina Brancaccio
Giovanni Battista Gaeta
Vincenzo Barnaba
Silvia Piconese
First published: 07 November 2020
https://doi.org/10.1111/liv.14720
Ilenia Pacella and Ilenia Cammarata equally contributing authors.
Handling editor: Benjamin Maasoumy

Funding information:

This work was supported by the International Network Institut Pasteur, Paris – ‘Programmes Transversaux de Recherche’ (PTR no. 20‐16 to SP and VB).
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Abstract
Background & Aims

During chronic viral infections, the apoptosis of activated T cell elicits a CD8+ T cell response directed to those cryptic epitopes that emerge from caspase‐cleaved structural proteins. Such response directed to apoptosis‐associated epitopes (AEs) contributes to the amplification of immunopathology.
Methods

Here, we have analysed through flow cytometry AE‐specific CD8+ T cells in patients with chronic hepatitis B virus (HBV) infection, naïve‐to‐treatment or undergoing nucleos(t)ide‐analogue (NUC) therapy.
Results

We found that AE‐specific CD8+ T cell frequencies were significantly increased only in those NUC‐treated patients who also presented advanced hepatic fibrosis. Regulatory T cells were also expanded in those patients, and AE‐specific, but not HBV‐specific, CD8+ T cell frequency positively correlated with Treg percentages. Through multiparameter flow cytometry, multidimensionality reduction and unsupervised clustering analysis, we could identify novel subpopulations among effector memory (em) and emCD45RA+ T cell (Tem and Temra) subsets. CD8+ T cells with distinct specificities differentially populated the subpopulation map: while HBV‐specific were mostly contained in the Tem subset, AE‐specific CD8+ T cells encompassed naïve, as well as T central memory, Tem and Temra cells.
Conclusion

All together, these findings indicate a link between AE‐specific CD8+ T cells and advanced liver fibrosis in patients with chronic HBV infection, and suggest that virus‐specific and AE‐specific CD8+ T cells exhibit distinct differentiation states and contribute in distinct ways to immunopathology.

StephenW

慢性HBV感染和纤维化患者特异性针对凋亡相关表位的CD8 + T细胞扩增
伊莱尼亚·帕切拉
伊莱尼亚·坎马拉塔（Ilenia Cammarata）
卡梅拉·马丁（Carmela Martire）
朱塞佩娜·布朗卡乔
乔凡尼·巴蒂斯塔·加埃塔
文森佐·巴纳巴（Vincenzo Barnaba）
西尔维亚·皮科尼斯（Silvia Piconese）
首次发布：2020年11月7日
https://doi.org/10.1111/liv.14720
Ilenia Pacella和Ilenia Cammarata同样是作者。
处理编辑：本杰明·马苏米

资金信息：

这项工作得到了巴黎国际巴斯德研究所的支持-“ Recherche跨国计划”（SP和VB的PTR第20-16号）。
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背景与目标

在慢性病毒感染期间，活化的T细胞的凋亡引起CD8 + T细胞应答，该应答针对那些从caspase裂解的结构蛋白中出现的隐性表位。这种针对凋亡相关表位（AE）的反应有助于免疫病理学的放大。
方法

在这里，我们通过流式细胞仪分析了慢性乙型肝炎病毒（HBV）感染，未接受过治疗或正在接受核苷酸（t）-类似物（NUC）治疗的患者的AE特异性CD8 + T细胞。
结果

我们发现，仅在那些同时出现晚期肝纤维化的接受NUC治疗的患者中，AE特异性CD8 + T细胞的频率显着增加。这些患者中的调节性T细胞也有所扩大，并且AE特异性而非HBV特异性CD8 + T细胞频率与Treg百分比呈正相关。通过多参数流式细胞术，多维降低和无监督聚类分析，我们可以识别效应记忆（em）和emCD45RA + T细胞（Tem和Temra）子集之间的新亚群。具有不同特异性的CD8 + T细胞差异性地分布在亚人群图上：虽然HBV特异性大多数包含在Tem亚群中，但AE特异性CD8 + T细胞涵盖了幼稚的以及T中枢记忆，Tem和Temra细胞。
结论

总之，这些发现表明，慢性HBV感染患者的AE特异性CD8 + T细胞与晚期肝纤维化之间存在联系，并表明病毒特异性CD8 + T细胞表现出不同的分化状态，并以不同的方式参与免疫病理学研究。 。