ArticlePloS one2014
CD4+ primary T cells expressing HCV-core protein upregulate Foxp3 and IL-10, suppressing CD4 and CD8 T cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Mechanisms of Interleukin-10-Mediated Immunosuppression in Viral Infections.Pathogens (Basel, Switzerland) · 2025Review
- Unveiling the nexus between direct-acting antivirals in hepatitis C virus elimination and immune response.Clinical and experimental medicine · 2025Review
- A short hepatitis C virus NS5A peptide expression by AAV vector modulates human T cell activation and reduces vector immunogenicity.Gene therapy · 2022Article
- The Role of Glycosyltransferases in Colorectal Cancer.International journal of molecular sciences · 2021Review
- Immune Checkpoints in Viral Infections.Viruses · 2020Review
- Lipid Microbubble-Conjugated Anti-CD3 and Anti-CD28 Antibodies (Microbubble-Based Human T Cell Activator) Offer Superior Long-Term Expansion of Human Naive T Cells In Vitro.ImmunoHorizons · 2020Article
- Direct-acting antiviral treatment downregulates immune checkpoint inhibitor expression in patients with chronic hepatitis C.Clinical and experimental medicine · 2020Article
- Model of the adaptive immune response system against HCV infection reveals potential immunomodulatory agents for combination therapy.Scientific reports · 2018Article
- Immune checkpoint inhibition: prospects for prevention and therapy of hepatocellular carcinoma.Clinical & translational immunology · 2017Review
- T-bet-mediated Tim-3 expression dampens monocyte function during chronic hepatitis C virus infection.Immunology · 2017Article
- Ultrastructural Localization and Molecular Associations of HCV Capsid Protein in Jurkat T Cells.Frontiers in microbiology · 2017Article
- Inflammatory status in human hepatic cirrhosis.World journal of gastroenterology · 2015Review
- Hepatitis C virus core protein triggers expansion and activation of CD4(+)CD25(+) regulatory T cells in chronic hepatitis C patients.Cellular & molecular immunology · 2015Article
- Expression profile and kinetics of cytokines and chemokines in patients with chronic hepatitis C.International journal of clinical and experimental medicine · 2015Article
- Article
- Regulatory T cells contribute to the recovery of acute lung injury by upregulating Tim-3.Inflammation · 2015Article
- Human Umbilical Cord Mesenchymal Stem Cells Inhibit the Function of Allogeneic Activated Vγ9Vδ2 T Lymphocytes In Vitro.BioMed research international · 2015Article
- Hepatitis C virus core protein enhances HIV-1 replication in human macrophages through TLR2, JNK, and MEK1/2-dependent upregulation of TNF-α and IL-6.FEBS letters · 2014Article
- P selectins and immunological profiles in HCV and Schistosoma mansoni induced chronic liver disease.BMC gastroenterology · 2014Article
- Genetic variants in human leukocyte antigen-DP influence both hepatitis C virus persistence and hepatitis C virus F protein generation in the Chinese Han population.International journal of molecular sciences · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adaptive T cell responses are critical for controlling HCV infection. While there is clinical evidence of a relevant role for regulatory T cells in chronic HCV-infected patients, based on their increased number and function; mechanisms underlying such a phenomena are still poorly understood. Accumulating evidence suggests that proteins from Hepatitis C virus can suppress host immune responses. We and others have shown that HCV is present in CD4+ lymphocytes from chronically infected patients and that HCV-core protein induces a state of unresponsiveness in the CD4+ tumor cell line Jurkat. Here we show that CD4+ primary T cells lentivirally transduced with HCV-core, not only acquire an anergic phenotype but also inhibit IL-2 production and proliferation of bystander CD4+ or CD8+ T cells in response to anti-CD3 plus anti-CD28 stimulation. Core-transduced CD4+ T cells show a phenotype characterized by an increased basal secretion of the regulatory cytokine IL-10, a decreased IFN-γ production upon stimulation, as well as expression of regulatory T cell markers, CTLA-4, and Foxp3. A significant induction of CD4+CD25+CD127(low)PD-1(high)TIM-3(high) regulatory T cells with an exhausted phenotype was also observed. Moreover, CCR7 expression decreased in HCV-core expressing CD4+ T cells explaining their sequestration in inflamed tissues such as the infected liver. This work provides a new perspective on de novo generation of regulatory CD4+ T cells in the periphery, induced by the expression of a single viral protein.
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