ArticleJournal of immunology (Baltimore, Md. : 1950)2014
KLRG1 impairs CD4+ T cell responses via p16ink4a and p27kip1 pathways: role in hepatitis B vaccine failure in individuals with hepatitis C virus infection.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- T Cell Immunosenescence in Inflammatory Skin Diseases: Pathogenesis and Therapeutic Targets.Aging cell · 2026Review
- ATM in immunobiology: From lymphocyte development to cancer immunotherapy.Translational oncology · 2025Review
- A Comprehensive Review of Hepatitis B Vaccine Nonresponse and Associated Risk Factors.Vaccines · 2024Review
- The role of KLRG1: a novel biomarker and new therapeutic target.Cell communication and signaling : CCS · 2024Review
- Decreased antibody response to influenza vaccine with an enhanced antibody response to subsequent SARS-CoV-2 vaccination in patients with chronic hepatitis B virus infection.Immunity, inflammation and disease · 2023Article
- The presence of senescent peripheral T-cells is negatively correlated to COVID-19 vaccine-induced immunity in cancer patients under 70 years of age.Frontiers in immunology · 2023Article
- Mitochondrial topoisomerase 1 inhibition induces topological DNA damage and T cell dysfunction in patients with chronic viral infection.Frontiers in cellular and infection microbiology · 2022Article
- The Yin and Yang of Targeting KLRG1Frontiers in immunology · 2022Review
- Immune Activation Induces Telomeric DNA Damage and Promotes Short-Lived Effector T Cell Differentiation in Chronic HCV Infection.Hepatology (Baltimore, Md.) · 2021Article
- The hedgehog pathway suppresses neuropathogenesis in CD4 T cell-driven inflammation.Brain : a journal of neurology · 2021Article
- Oxidative Stress Induces Mitochondrial Compromise in CD4 T Cells From Chronically HCV-Infected Individuals.Frontiers in immunology · 2021Article
- Risk Factors and Prevention of Viral Hepatitis-Related Hepatocellular Carcinoma.Frontiers in oncology · 2021Review
- CRELD1 modulates homeostasis of the immune system in mice and humans.Nature immunology · 2020Article
- Review
- Disruption of Telomere Integrity and DNA Repair Machineries by KML001 Induces T Cell Senescence, Apoptosis, and Cellular Dysfunctions.Frontiers in immunology · 2019Article
- Topological DNA damage, telomere attrition and T cell senescence during chronic viral infections.Immunity & ageing : I & A · 2019Article
- Inhibition of TRF2 accelerates telomere attrition and DNA damage in naïve CD4 T cells during HCV infection.Cell death & disease · 2018Article
- Article
- HCV-associated exosomes promote myeloid-derived suppressor cell expansion via inhibiting miR-124 to regulate T follicular cell differentiation and function.Cell discovery · 2018Article
- Insufficiency of DNA repair enzyme ATM promotes naive CD4 T-cell loss in chronic hepatitis C virus infection.Cell discovery · 2018Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Coinfection of hepatitis B virus (HBV) with hepatitis C virus (HCV) is quite common, leading to an increase in morbidity and mortality. As such, HBV vaccination is recommended in HCV-infected individuals. However, HBV vaccine responses in HCV-infected individuals are often blunted compared with uninfected populations. The mechanism for this failure of vaccine response in HCV-infected subjects remains unclear. In this study, we investigated the expression and function of an inhibitory receptor, killer cell lectin-like receptor subfamily G member 1 (KLRG1), in the regulation of CD4(+) T cells and HBV vaccine responses during HCV infection. We demonstrated that KLRG1 was overexpressed on CD4(+) T cells from HCV-infected, HBV vaccine nonresponders compared with HBV vaccine responders. The capacity of CD4(+) T cells to proliferate and secrete IL-2 cytokine was inversely associated with the level of KLRG1 expression. Importantly, blocking KLRG1 signaling resulted in a significant improvement in CD4(+) T cell proliferation and IL-2 production in HCV-infected, HBV vaccine nonresponders in response to TCR stimulation. Moreover, blockade of KLRG1 increased the phosphorylation of Akt (Ser(473)) and decreased the expression of cell cycle inhibitors p16(ink4a) and p27(kip1), which subsequently enhanced the expression of cyclin-dependent kinase 2 and cyclin E. These results suggest that the KLRG1 pathway impairs CD4(+) T cell responses to neoantigen and induces a state of immune senescence in individuals with HCV infection, raising the possibility that blocking this negative-signaling pathway might improve HBV vaccine responses in the setting of chronic viral infection.
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Registered trials
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