ArticleThe Journal of experimental medicine2014
Dysfunctional CD8+ T cells in hepatitis B and C are characterized by a lack of antigen-specific T-bet induction.
Article in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 107 citations in OpenAlex.
- PD-1 blockade partially recovers dysfunctional virus-specific B cells in chronic hepatitis B infection.The Journal of clinical investigation · 2018Trial
- Temporal Dynamics of CD8+ T Cell Effector Responses during Primary HIV Infection.PLoS pathogens · 2016Trial
- Article
- T cell adaptation in chronic infections and tumors.Cellular & molecular immunology · 2026Review
- Targets of protective immunity and opportunities in hepatitis C virus vaccine development.Nature reviews. Immunology · 2026Review
- Stable characteristics of intrapopulation heterogeneity in virus-specific Th1 cells during chronic viral challenge infection.bioRxiv : the preprint server for biology · 2025Article
- High antigen burden drives CD8+ T cell dysfunction in a mouse model of chronic hepatitis B virus infection.Journal of virology · 2025Article
- Stable characteristics of intrapopulation heterogeneity in virus-specific Th1 cells during chronic viral challenge infection.Frontiers in immunology · 2025Article
- Article
- Attenuated effector T cells are linked to control of chronic HBV infection.Nature immunology · 2024Article
- Article
- Hepatitis C virus modified sE2Journal of virology · 2024Article
- Dysfunction and regulatory interplay of T and B cells in chronic hepatitis B: immunotherapy and emerging antiviral strategies.Frontiers in cellular and infection microbiology · 2024Review
- Development of a CD8Heliyon · 2023Article
- Human circulating and tissue-resident memory CD8Nature immunology · 2023Review
- Advances in Immunotherapy for Hepatitis B.Pathogens (Basel, Switzerland) · 2022Review
- Innate and adaptive immune escape mechanisms of hepatitis B virus.World journal of gastroenterology · 2022Review
- Transcriptional Pattern Analysis of Virus-Specific CD8+ T Cells in Hepatitis C Infection: Increased Expression of TOX and Eomesodermin During and After Persistent Antigen Recognition.Frontiers in immunology · 2022Article
- Advances in designing Adeno-associated viral vectors for development of anti-HBV gene therapeutics.Virology journal · 2021Review
- Hepatitis B virus polymerase-specific T cell epitopes shift in a mouse model of chronic infection.Virology journal · 2021Article
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16 authors at 7 institutions in 2 countries.
Funding
Abstract
The transcription factor T-bet regulates the production of interferon-γ and cytotoxic molecules in effector CD8 T cells, and its expression correlates with improved control of chronic viral infections. However, the role of T-bet in infections with differential outcome remains poorly defined. Here, we report that high expression of T-bet in virus-specific CD8 T cells during acute hepatitis B virus (HBV) and hepatitis C virus (HCV) infection was associated with spontaneous resolution, whereas T-bet deficiency was more characteristic of chronic evolving infection. T-bet strongly correlated with interferon-γ production and proliferation of virus-specific CD8 T cells, and its induction by antigen and IL-2 stimulation partially restored functionality in previously dysfunctional T-bet-deficient CD8 T cells. However, restoration of a strong interferon-γ response required additional stimulation with IL-12, which selectively induced the phosphorylation of STAT4 in T-bet(+) CD8 T cells. The observation that T-bet expression rendered CD8 T cells responsive to IL-12 suggests a stepwise mechanism of T cell activation in which T-bet facilitates the recruitment of additional transcription factors in the presence of key cytokines. These findings support a critical role of T-bet for viral clearance and suggest T-bet deficiency as an important mechanism behind chronic infection.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.