Abstract:
BACKGROUND & AIMS:The 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. METHODS:Through 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. RESULTS:TNF-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. CONCLUSIONS:HBV-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 SUMMARY:TNF-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.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Wang H,Luo H,Wan X,Fu X,Mao Q,Xiang X,Zhou Y,He W,Zhang J,Guo Y,Tan W,Deng Gdoi
10.1016/j.jhep.2019.08.024subject
Has Abstractpub_date
2020-01-01 00:00:00pages
45-56issue
1eissn
0168-8278issn
1600-0641pii
S0168-8278(19)30517-3journal_volume
72pub_type
杂志文章abstract:BACKGROUND/AIMS:During liver regeneration, a network of cytokines and growth factors interact with hepatocytes, helping to restore the liver mass and functions after partial tissue loss. Agonists that trigger Ca2+ signals in the liver contribute to this process, although little is known about calcium signalling during ...
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更新日期:1997-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/0168-8278(89)90051-2
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doi:10.1016/s0168-8278(05)80009-1
更新日期:1993-04-01 00:00:00
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pub_type: 临床试验,杂志文章,多中心研究
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pub_type: 杂志文章
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journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2007.01.021
更新日期:2007-06-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
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更新日期:2003-02-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
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更新日期:1998-01-01 00:00:00
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更新日期:2006-02-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 杂志文章
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更新日期:1990-01-01 00:00:00
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journal_title:Journal of hepatology
pub_type: 评论,杂志文章
doi:10.1016/j.jhep.2010.02.003
更新日期:2010-06-01 00:00:00
abstract:BACKGROUND & AIMS:We used longitudinal data from the ANRS CO13 HEPAVIH cohort study of HIV-HCV co-infected individuals to investigate whether polyphenol rich food intake through coffee and/or daily chocolate consumption could play a role in reducing liver enzymes levels. METHODS:Longitudinal data collection included s...
journal_title:Journal of hepatology
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更新日期:2014-01-01 00:00:00