ArticleProceedings of the National Academy of Sciences of the United States of America2013
Liver type I regulatory T cells suppress germinal center formation in HBV-tolerant mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02505009 (Efficacy of HBV Therapeutic Vaccine in Consolidation of Nucleos), which is not on this map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Efficacy of HBV Therapeutic Vaccine in Consolidation of Nucleos(t)Ide Analogues Therapy: a Pilot Study
Who cites it
22 citing papers in PubMed, 45 citations in OpenAlex.
- [Research progress on B cells in chronic hepatitis B].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- Gut microbiota trigger host liver immune responses that affect drug-metabolising enzymes.Frontiers in immunology · 2024Review
- The novel mechanism facilitating chronic hepatitis B infection: immunometabolism and epigenetic modification reprogramming.Frontiers in immunology · 2024Review
- CpG-C ODN M362 as an immunoadjuvant for HBV therapeutic vaccine reverses the systemic tolerance against HBV.International journal of biological sciences · 2022Article
- B Cell-mediated Humoral Immunity in Chronic Hepatitis B Infection.Journal of clinical and translational hepatology · 2021Review
- Functional heterogeneity of CD4Seminars in immunopathology · 2021Review
- The Yin and Yang of Type 1 Regulatory T Cells: From Discovery to Clinical Application.Frontiers in immunology · 2021Review
- Article
- The Multiple Functions of B Cells in Chronic HBV Infection.Frontiers in immunology · 2020Review
- Complexity of immune responses to AAV transgene products - Example of factor IX.Cellular immunology · 2019Review
- Maternal Immunity Influences Vertical Transmission of Hepatitis B to Newborns.Hepatology communications · 2019Article
- CD4Frontiers in immunology · 2019Article
- The doses of plasmid backbone plays a major role in determining the HBV clearance in hydrodynamic injection mouse model.Virology journal · 2018Article
- Technical Improvement and Application of Hydrodynamic Gene Delivery in Study of Liver Diseases.Frontiers in pharmacology · 2017Review
- Interferon-γ facilitates hepatic antiviral T cell retention for the maintenance of liver-induced systemic tolerance.The Journal of experimental medicine · 2016Article
- Clearing Persistent Extracellular Antigen of Hepatitis B Virus: An Immunomodulatory Strategy To Reverse Tolerance for an Effective Therapeutic Vaccination.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Liver sinusoidal endothelial cells induce tolerance of autoreactive CD4+ recent thymic emigrants.Scientific reports · 2016Article
- Hepatitis B Virus Infection Rate and Distribution in Chinese Systemic Lupus Erythematosus Patients.Medical science monitor : international medical journal of experimental and clinical research · 2015Article
- Inadequate activation of the HBsAg-specific Th cells by APCs leads to hyporesponsiveness to HBsAg vaccine in B10.S mice.Human vaccines & immunotherapeutics · 2015Article
- Therapeutic strategies for a functional cure of chronic hepatitis B virus infection.Acta pharmaceutica Sinica. B · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The liver plays a critical role in inducing systemic immune tolerance, for example, during limiting hypersensitivity to food allergy and in rendering acceptance of allotransplant or even hepatotropic pathogens. We investigated the unknown mechanisms of liver tolerance by using an established hepatitis B virus (HBV)-carrier mouse model, and found that these mice exhibited an antigen-specific tolerance toward peripheral HBsAg vaccination, showing unenlarged draining lymph node (DLN), lower number of germinal centers (GC), and inactivation of GC B cells and follicular T helper (Tfh) cells. Both in vivo and in vitro immune responses toward HBsAg were suppressed by mononuclear cells from HBV-carrier mice, which were CD4(+) Foxp3(-) type 1 regulatory T (Tr1)-like cells producing IL-10. Using recipient Rag1(-/-) mice, hepatic Tr1-like cells from day 7 of HBV-persistent mice acquired the ability to inhibit anti-HBV immunity 3 d earlier than splenic Tr1-like cells, implying that hepatic Tr1-like cells were generated before those in spleen. Kupffer cell depletion or IL-10 deficiency led to impairment of Tr1-like cell generation, along with breaking HBV persistence. The purified EGFP(+)CD4(+) T cells (containing Tr1-like cells) from HBV-carrier mice trafficked in higher numbers to DLN in recipient mice after HBsAg vaccination, and subsequently inactivated both Tfh cells and GC B cells via secreting IL-10, resulting in impaired GC formation and anti-HB antibody production. Thus, our results indicate Tr1-like cells migrate from the liver to the DLN and inhibit peripheral anti-HBV immunity by negatively regulating GC B cells and Tfh cells.
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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.