Impact of HBsAg and HBcrAg levels on phenotype and function of HBV-specific T cells in patients with chronic hepatitis B virus infection.
Impact of HBsAg and HBcrAg levels on phenotype and function of HBV-specific T cells in patients with chronic hepatitis B virus infection.
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慢性B型肝炎患者HBsAg和HBcrAg水平对HBV特异性T细胞表型和功能的影响
DOI：
10.1136/gutjnl-2021-324646
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发表时间：
2022-11
期刊：
影响因子：
24.5
通讯作者：
Cornberg, Markus
中科院分区：
文献类型：
--
作者：
Aliabadi, Elmira;Urbanek-Quaing, Melanie;Maasoumy, Benjamin;Bremer, Birgit;Grasshoff, Martin;Li, Yang;Niehaus, Christian E.;Wedemeyer, Heiner;Kraft, Anke R. M.;Cornberg, Markus
乙型肝炎病毒（HBV）特异性T细胞是控制HBV感染的主要效应细胞，乙型肝炎表面抗原（HBsAg）被认为是免疫应答受损的关键因素，这是慢性HBV感染的一个标志。除HBsAg外，其他病毒标志物如乙型肝炎核心相关抗原（HBcrAg）也可用，但它们与HBV特异性免疫反应的潜在关联尚未确定，如果这些标志物用于针对HBV功能性治愈的新疗法的患者分层，这将是重要的。我们分析了92例乙型肝炎e抗原阴性慢性HBV感染患者不同HBsAg和HBcrAg水平的T细胞反应。采用重叠肽进行体外反应分析（n=57），并对人白细胞抗原(HLA)-A*02患者（n=35）的HBV core18特异性和聚合酶（pol）455特异性CD8+ T细胞进行评估。此外，我们还研究了抗程序性细胞死亡配体1 （anti-PD-L1）的体外反应性。hbv特异性T细胞反应不受HBsAg水平的影响，而受年龄的影响，CD4+ T细胞反应在低HBsAg水平的患者中最高。HBV core18特异性和pol455特异性CD8+ T细胞的表型和功能不同，但HBsAg和HBcrAg水平不影响它们的表型和功能。用抗pd - l1阻断可以恢复hbv特异性T细胞，但在低HBsAg，特别是低HBcrAg患者分离的T细胞中效果明显更高。我们的数据表明，年龄和HBcrAg而不是HBsAg与hbv特异性T细胞反应相关。最后，HBsAg，特别是HBcrAg显示的非常低的抗原水平可能影响T细胞对检查点抑制的反应。
Hepatitis B virus (HBV)-specific T cells are main effector cells in the control of HBV infection and hepatitis B surface antigen (HBsAg) is suggested to be a critical factor in the impaired immune response, a hallmark of chronic HBV infection. In addition to HBsAg, other viral markers such as hepatitis B core-related antigen (HBcrAg) are available, but their potential association with HBV-specific immune responses is not defined yet, which will be important if these markers are used for patient stratification for novel therapies aimed at functional HBV cure. We analysed T cell responses in 92 patients with hepatitis B e antigen negative chronic HBV infection with different HBsAg and HBcrAg levels. Overlapping peptides were used for in vitro response analyses (n=57), and HBV core18-specific and polymerase (pol)455-specific CD8+ T cells were assessed in human leukocyte antigen (HLA)-A*02 patients (n=35). In addition, in vitro responsiveness to anti-programmed cell death-ligand 1 (anti-PD-L1) was investigated. HBV-specific T cell responses were not affected by HBsAg levels, but rather by age and CD4+ T cell responses were highest in patients with low HBcrAg levels. The phenotypes and functionality of HBV core18-specific and pol455-specific CD8+ T cells differed, but HBsAg and HBcrAg levels did not affect their profiles. Blocking with anti-PD-L1 could restore HBV-specific T cells, but the effect was significantly higher in T cells isolated from patients with low HBsAg and in particular low HBcrAg. Our data suggest that age and HBcrAg rather than HBsAg, are associated with HBV-specific T cell responses. Finally, very low antigen levels indicated by HBsAg and in particular HBcrAg may influence T cell response to checkpoint inhibition.
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DOI：
10.1084/jem.20200298
发表时间：
2020-11-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fumagalli V;Di Lucia P;Venzin V;Bono EB;Jordan R;Frey CR;Delaney W;Chisari FV;Guidotti LG;Iannacone M
通讯作者：
Iannacone M
影响因子：
15.3
作者：
Das, Abhishek;Hoare, Matthew;Davies, Nathan;Lopes, A. Ross;Dunn, Claire;Kennedy, Patrick T. F.;Alexander, Graeme;Finney, Helene;Lawson, Alistair;Plunkett, Fiona J.;Bertoletti, Antonio;Akbar, Arne N.;Maini, Mala K.
通讯作者：
Maini, Mala K.
影响因子：
13.5
作者：
Cornberg, Markus;Lok, Anna Suk-Fong;Zoulim, Fabien
通讯作者：
Zoulim, Fabien
影响因子：
2.7
作者：
Weinberger, Birgit;Lazuardi, Lutfan;Grubeck-Loebenstein, Beatrix
通讯作者：
Grubeck-Loebenstein, Beatrix
影响因子：
4.6
作者：
Wiegand, Steffen B.;Beggel, Bastian;Cornberg, Markus
通讯作者：
Cornberg, Markus