ArticleThe Journal of clinical investigation2009
PD-L1 negatively regulates CD4+CD25+Foxp3+ Tregs by limiting STAT-5 phosphorylation in patients chronically infected with HCV.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 papers.
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Who cites it
175 citing papers in PubMed.
- The altered PD-1/PD-L1 pathway delivers the 'one-two punch' effects to promote the Treg/Th17 imbalance in pre-eclampsia.Cellular & molecular immunology · 2018Trial
- Therapeutic DNA vaccination using in vivo electroporation followed by standard of care therapy in patients with genotype 1 chronic hepatitis C.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Trial
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- Antineoplastic agents-associated hepatitis B virus reactivation: Research progress and molecular mechanisms.Virus research · 2025Review
- HBV reactivation and prognosis after systemic therapy in HCC with undetectable HBV DNA: a multicenter retrospective study.Scientific reports · 2025Article
- T Regulatory Mechanisms in Airway and Interstitial Lung Disease.Seminars in respiratory and critical care medicine · 2025Review
- Regulatory T cell and endothelial cell crosstalk.Nature reviews. Immunology · 2025Review
- PD-1 receptor deficiency enhances CD30Nature immunology · 2025Article
- HBV reactivation and its management in HBV-related HCC patients undergoing HAIC-TKI-ICI therapy: A multicenter study.iScience · 2025Article
- Microchimerism and pregnancy complications with placental dysfunction.Seminars in immunopathology · 2025Review
- Mineralocorticoid receptor antagonism partially prevents dysfunction of T cell maturation in rats chronically treated with ethanol.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Drug-Induced Liver Injury Associated With Emerging Cancer Therapies.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Hepatitis B virus reactivation in hepatocellular carcinoma patients after hepatic arterial infusion chemotherapy combined with and without immunotherapy.Infectious agents and cancer · 2024Article
- Exhaustion of T cells after renal transplantation.Frontiers in immunology · 2024Review
- Possibility of PD-1/PD-L1 Inhibitors for the Treatment of Patients with Chronic Hepatitis B Infection.Digestive diseases (Basel, Switzerland) · 2024Review
- Programmed cell death-1 is involved with peripheral blood immune cell profiles in patients with hepatitis C virus antiviral therapy.PloS one · 2024Article
- Hepatitis C Virus and the Host: A Mutual Endurance Leaving Indelible Scars in the Host's Immunity.International journal of molecular sciences · 2023Review
- Sequencing Systemic Therapy in Hepatocellular Carcinoma.Current treatment options in oncology · 2023Review
115 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD4+CD25+Foxp3+ Tregs suppress autoimmune responses. In addition, they limit T cell responses during chronic infection, thereby minimizing T cell-dependent immunopathology. We sought to investigate how Tregs are regulated in the livers of patients chronically infected with HCV, where they control the balance between an adequate protective immune response and suppression of immunopathology. We found that, despite accumulating and proliferating at sites of infection in the livers of patients chronically infected with HCV, Tregs were relatively less expanded than CD4+CD25+Foxp3- effector T cells. The relative lower expansion of intrahepatic Tregs coincided with their upregulation of programmed death-1 (PD-1). PD-1 expression inversely correlated with both Treg proliferation and clinical markers of immune suppression in vivo. Consistent with the possibility that PD-1 controls Tregs, blockade of the interaction between PD-1 and programmed death-1 ligand 1 (PD-L1) enhanced the in vitro expansion and function of Tregs isolated from the livers of patients chronically infected with HCV. Blockade of the interaction between PD-L1 and B7.1 also improved the proliferation of these cells. Interestingly, both PD-1 and phosphorylated STAT-5 were overexpressed in intrahepatic Tregs in a parallel fashion in steady disease conditions, and in an alternate-fluctuating fashion during the course of severe hepatitis reactivation. Notably, PD-L1 blockade upregulated STAT-5 phosphorylation in Tregs ex vivo. These data suggest that PD-L1 negatively regulates Tregs at sites of chronic inflammation by controlling STAT-5 phosphorylation.
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