HBV特异性CD4 T细胞的TNF-α/IFN-γ谱与慢性HBV感染中的肝损伤和

StephenW

TNF-α/IFN-γ profile of HBV-specific CD4 T cells is associated with liver damage and viral clearance in chronic HBV infection [url=]Haoliang Wang[/url]1,†
,  [url=]Heng Luo[/url]1,†
,  [url=]Xing Wan[/url]1,†
,  [url=]Xiaolan Fu[/url]2
,  [url=]Qing Mao[/url]1
,  [url=]Xiaomei Xiang[/url]1
,  [url=]Yi Zhou[/url]1
,  [url=]Weiwei He[/url]1
,  [url=]Juan Zhang[/url]1
,  [url=]Yanzhi Guo[/url]1
,  [url=]Wenting Tan[/url]1,,[url=]Correspondence information about the author  Wenting Tan[/url]Email the author  Wenting Tan
,  [url=]Guohong Deng[/url]1,,[url=]Correspondence information about the author  Guohong Deng[/url]Email the author  Guohong Deng

See Editorial, pages 9–11




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DOI: https://doi.org/10.1016/j.jhep.2019.08.024 |

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Highlights

• •TNF-α producing cells are the dominant population of HBV-specific CD4 T cells in chronic HBV infection.
• •Increased frequency/dominance of HBV-specific IFN-γ producing CD4 T cells parallels elevated HBV viral clearance.
• •HBV core-specific TNF-α producing CD4 T cells are associated with liver damage in patients with a hepatitis B flare.
• •HBV-specific IFN-γ producing CD4 T cells are associated with HBV viral clearance in patients with a hepatitis B flare.
• •Some HBV-specific IFN-γ producing CD4 T cells might originate from HBV-specific TNF-α producing CD4 T cells during flare.
  

Background & AimsThe role of hepatitis B virus (HBV)-specific CD4 T cells in patients with chronic HBV infection is not clear. Thus, we aimed to elucidate this in patients with chronic infection, and those with hepatitis B flares.


MethodsThrough intracellular IFN-γ and TNF-α staining, HBV-specific CD4 T cells were analyzed in 68 patients with chronic HBV infection and alanine aminotransferase (ALT) <2x the upper limit of normal (ULN), and 28 patients with a hepatitis B flare. HBV-specific HLA-DRB1*0803/HLA-DRB1*1202-restricted CD4 T cell epitopes were identified.


ResultsTNF-α producing cells were the dominant population in patients’ HBV-specific CD4 T cells. In patients with ALT <2xULN, both the frequency and the dominance of HBV-specific IFN-γ producing CD4 T cells increased sequentially in patients with elevated levels of viral clearance: HBV e antigen (HBeAg) positive, HBeAg negative, and HBV surface antigen (HBsAg) negative. In patients with a hepatitis B flare, the frequency of HBV core-specific TNF-α producing CD4 T cells was positively correlated with patients’ ALT and total bilirubin levels, and the frequency of those cells changed in parallel with the severity of liver damage. Patients with HBeAg/HBsAg loss after flare showed higher frequency and dominance of HBV-specific IFN-γ producing CD4 T cells, compared to patients without HBeAg/HBsAg loss. Both the frequency and the dominance of HBV S-specific IFN-γ producing CD4 T cells were positively correlated with the decrease of HBsAg during flare. A differentiation process from TNF-α producing cells to IFN-γ producing cells in HBV-specific CD4 T cells was observed during flare. Eight and 9 HBV-derived peptides/pairs were identified as HLA-DRB1*0803 restricted epitopes and HLA-DRB1*1202 restricted epitopes, respectively.


ConclusionsHBV-specific TNF-α producing CD4 T cells are associated with liver damage, while HBV-specific IFN-γ producing CD4 T cells are associated with viral clearance in patients with chronic HBV infection.


Lay summaryTNF-α producing cells are the dominant population of hepatitis B virus (HBV)-specific CD4 T cells in patients with chronic HBV infection. This population of cells might contribute to the aggravation of liver damage in patients with a hepatitis B flare. HBV-specific IFN-γ producing CD4 T cells are associated with HBV viral clearance. Differentiation from HBV-specific TNF-α producing CD4 T cells into HBV-specific IFN-γ producing CD4 T cells might favor HBV viral clearance.



Keywords:                [url=https://www.journal-of-hepatology.eu/action/doSearch?searchType=quick&occurrences=all<rlSrch=true&searchScope=fullSite&searchText=Hepatitis B virus&code=jhepat-site]Hepatitis B virus[/url], [url=https://www.journal-of-hepatology.eu/action/doSearch?searchType=quick&occurrences=all<rlSrch=true&searchScope=fullSite&searchText=CD4 T cells&code=jhepat-site]CD4 T cells[/url], [url=https://www.journal-of-hepatology.eu/action/doSearch?searchType=quick&occurrences=all<rlSrch=true&searchScope=fullSite&searchText=Liver damage&code=jhepat-site]Liver damage[/url], [url=https://www.journal-of-hepatology.eu/action/doSearch?searchType=quick&occurrences=all<rlSrch=true&searchScope=fullSite&searchText=Viral clearance&code=jhepat-site]Viral clearance[/url], Epitope

StephenW

HBV特异性CD4 T细胞的TNF-α/IFN-γ谱与慢性HBV感染中的肝损伤和病毒清除有关
王浩亮1，†
，罗衡1，†
，星湾1，†
傅小兰2
，青茂1
，向小梅1
一舟1
，何为伟1
张Juan
郭彦之1
，Tan Wenting1，low asterisk，'有关作者Wenting Tan的通讯信息给作者Wenwen Tan发电子邮件
，邓国宏1，低星号，'作者郭国宏的书信信息给作者郭国宏发电子邮件
见社论，第9-11页
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DOI：https：//doi.org/10.1016/j.jhep.2019.08.024 |
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强调

    •产生TNF-α的细胞是慢性HBV感染中HBV特异性CD4 T细胞的主要种群。
    •产生HBV特异性IFN-γ的CD4 T细胞的频率/优势增加，与HBV病毒清除率升高平行。
    •乙型肝炎发作患者中，产生HBV核心特异性TNF-α的CD4 T细胞与肝损害有关。
    •乙型肝炎爆发患者中，产生HBV特异性IFN-γ的CD4 T细胞与HBV病毒清除相关。
    •在爆发期间，某些产生HBV的IFN-γCD4 T细胞可能起源于产生HBV的TNF-αCD4 T细胞。

背景与目标

尚不清楚乙型肝炎病毒（HBV）特异性CD4 T细胞在慢性HBV感染患者中的作用。因此，我们的目的是在患有慢性感染的患者以及患有乙型肝炎的患者中阐明这一点。
方法

通过细胞内IFN-γ和TNF-α染色，对68例慢性HBV感染且丙氨酸转氨酶（ALT）<正常上限（ULN）上限的2倍的患者和28例乙型肝炎患者的HBV特异性CD4 T细胞进行了分析。耀斑。鉴定了HBV特异性HLA-DRB1 * 0803 / HLA-DRB1 * 1202限制性CD4 T细胞表位。
结果

产生TNF-α的细胞是患者HBV特异性CD4 T细胞的主要种群。在ALT <2xULN的患者中，病毒清除率升高的患者中，产生HBV特异性IFN-γ的CD4 T细胞的频率和优势依次增加：HBV e抗原（HBeAg）阳性，HBeAg阴性和HBV表面抗原（HBsAg）阴性。在患有乙型肝炎的患者中，产生HBV核心的TNF-α的CD4 T细胞的频率与患者的ALT和总胆红素水平呈正相关，并且这些细胞的频率与肝损害的严重程度平行变化。与没有HBeAg / HBsAg丢失的患者相比，爆发后HBeAg / HBsAg丢失的患者显示出更高的频率和优势，产生HBV特异性IFN-γ的CD4 T细胞。产生HBV S特异性IFN-γ的CD4 T细胞的频率和优势与爆发期间HBsAg的减少呈正相关。在爆发期间观察到了在HBV特异性CD4 T细胞中从产生TNF-α的细胞分化为产生IFN-γ的细胞的过程。八个和九个HBV衍生肽/对分别被鉴定为HLA-DRB1 * 0803限制性表位和HLA-DRB1 * 1202限制性表位。
结论

在患有慢性HBV感染的患者中，产生HBV的TNF-α的CD4 T细胞与肝损伤相关，而产生HBV的IFN-γ的CD4 T细胞与病毒清除率相关。
放置摘要

在患有慢性HBV感染的患者中，产生TNF-α的细胞是乙型肝炎病毒（HBV）特异性CD4 T细胞的主要种群。这种细胞群可能会加剧乙型肝炎爆发患者的肝损伤。产生HBV的IFN-γCD4 T细胞与HBV病毒清除有关。从产生HBV的TNF-α的CD4 T细胞分化为产生HBV的IFN-γ的CD4 T细胞可能有助于HBV病毒清除。
关键字：
乙型肝炎病毒，CD4 T细胞，肝损伤，病毒清除，抗原决定簇