ArticleThe Journal of experimental medicine2013
Up-regulation of a death receptor renders antiviral T cells susceptible to NK cell-mediated deletion.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 184 papers.
What it found
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Who cites it
184 citing papers in PubMed, 339 citations in OpenAlex.
- Therapeutic Potential of TLR8 Agonist GS-9688 (Selgantolimod) in Chronic Hepatitis B: Remodeling of Antiviral and Regulatory Mediators.Hepatology (Baltimore, Md.) · 2021Trial
- Interferon Alpha Induces Sustained Changes in NK Cell Responsiveness to Hepatitis B Viral Load Suppression In Vivo.PLoS pathogens · 2016Trial
- Uncovering immune dysfunction in ACLF: Cellular mechanisms, molecular pathways, and therapeutic frontiers.Journal of hepatology · 2026Review
- Review
- Unconventional functions of natural killer cells in homeostasis and disease.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Dissecting antibody-mediated natural killer cell effects reveals a cytotoxic CX3CR1+KLRC2-CD16hi subset linked to hepatitis B virus outcomes.Clinical and molecular hepatology · 2026Article
- T-Cell Profiles in HBV Functional Cure and People Living With HIV: Known Knowns, Known Unknowns, and Unknown Unknowns.Current HIV/AIDS reports · 2026Review
- Expanded adaptive NKG2C+ NK cells exhibit potent ADCC and functional responses against HBV-infected hepatoma cell lines.Cytotherapy · 2026Article
- Targeting the innate immune system in treating hepatitis B: prospects for functional cure.Clinical and molecular hepatology · 2026Review
- From exhaustion to functional cure: frontiers in reversing HBV-specific T-cell immunity.Frontiers in immunology · 2026Review
- Interferon-mediated NK cell activation increases cytolytic activity against T follicular helper cells and limits antibody response to SARS-CoV-2.Nature immunology · 2025Article
- Natural killer cells and IFN-γ protect against liver injury during HAV infection in mice.Journal of virology · 2025Article
- Review
- Review
- The role of immune regulation in HBV infection and hepatocellular carcinogenesis.Frontiers in immunology · 2025Review
- Advance in molecular mechanisms underlying diabetes related to viral hepatitis infection.Frontiers in cellular and infection microbiology · 2025Review
- Anti-HBV treatment partially restores the dysfunction of innate immune cells and unconventional T cells during chronic HBV infection.Frontiers in immunology · 2025Review
- Immune Tolerance Regulation Is Critical to Immune Homeostasis.Journal of immunology research · 2025Review
- Inhibitory KIRs decrease HLA class II-mediated protection in Type 1 Diabetes.PLoS genetics · 2024Article
- Review
124 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Antiviral T cell responses in hepatotropic viral infections such as hepatitis B virus (HBV) are profoundly diminished and prone to apoptotic deletion. In this study, we investigate whether the large population of activated NK cells in the human liver contributes to this process. We show that in vitro removal of NK cells augments circulating CD8(+) T cell responses directed against HBV, but not against well-controlled viruses, in patients with chronic hepatitis B (CHB). We find that NK cells can rapidly eliminate HBV-specific T cells in a contact-dependent manner. CD8(+) T cells in the liver microcirculation are visualized making intimate contact with NK cells, which are the main intrahepatic lymphocytes expressing TNF-related apoptosis-inducing ligand (TRAIL) in CHB. High-level expression of the TRAIL death receptor TRAIL-R2 is found to be a hallmark of T cells exposed to the milieu of the HBV-infected liver in patients with active disease. Up-regulation of TRAIL-R2 renders T cells susceptible to caspase-8-mediated apoptosis, from which they can be partially rescued by blockade of this death receptor pathway. Our findings demonstrate that NK cells can negatively regulate antiviral immunity in chronic HBV infection and illustrate a novel mechanism of T cell tolerance in the human liver.
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Registered trials
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.