ArticlePLoS pathogens2013
IL-21 restricts virus-driven Treg cell expansion in chronic LCMV infection.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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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.
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Who cites it
44 citing papers in PubMed, 77 citations in OpenAlex.
- Immune Exhaustion in Chronic Infection and Cancer: Signaling Pathways and Therapeutic Interventions.MedComm · 2026Review
- Clone tracking through repeated malaria identifies high-fidelity memory CD4 T cell responses.Science immunology · 2025Article
- Differentiation and regulation of CD4Cellular and molecular life sciences : CMLS · 2024Review
- Enhanced abscopal anti-tumor response via a triple combination of thermal ablation, IL-21, and PD-1 inhibition therapy.Cancer immunology, immunotherapy : CII · 2024Article
- Review
- Engineered murine IL-21-secreting leukemia cells induce granzyme BCancer immunology, immunotherapy : CII · 2023Article
- Immunity to Cryptosporidium: Lessons from Acquired and Primary Immunodeficiencies.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- IL-21 signaling promotes the establishment of KSHV infection in human tonsil lymphocytes by increasing differentiation and targeting of plasma cells.Frontiers in immunology · 2022Article
- Regulatory T cells function in established systemic inflammation and reverse fatal autoimmunity.Nature immunology · 2021Article
- Genomic Spectrum and Phenotypic Heterogeneity of Human IL-21 Receptor Deficiency.Journal of clinical immunology · 2021Article
- Regulation of the germinal center and humoral immunity by interleukin-21.The Journal of experimental medicine · 2020Review
- Using two phases of the CD4 T cell response to blood-stage murine malaria to understand regulation of systemic immunity and placental pathology in Plasmodium falciparum infection.Immunological reviews · 2020Review
- Regulatory T Cell Development in the Thymus.Journal of immunology (Baltimore, Md. : 1950) · 2019Review
- T Cell-Intrinsic IL-6R Signaling Is Required for Optimal ICOS Expression and Viral Control during Chronic Infection.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Immune Exhaustion: Past Lessons and New Insights from Lymphocytic Choriomeningitis Virus.Viruses · 2019Review
- Linking Cell Dynamics With Gene Coexpression Networks to Characterize Key Events in Chronic Virus Infections.Frontiers in immunology · 2019Article
- Turning the Tide Against Regulatory T Cells.Frontiers in oncology · 2019Review
- Type I interferon signaling attenuates regulatory T cell function in viral infection and in the tumor microenvironment.PLoS pathogens · 2018Article
- Evaluating IL-21 as a Potential Therapeutic Target in Crohn's Disease.Gastroenterology research and practice · 2018Article
- T-Cell Exhaustion in Chronic Infections: Reversing the State of Exhaustion and Reinvigorating Optimal Protective Immune Responses.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 4 countries.
Funding
Abstract
Foxp3+ regulatory T (Treg) cells are essential for the maintenance of immune homeostasis and tolerance. During viral infections, Treg cells can limit the immunopathology resulting from excessive inflammation, yet potentially inhibit effective antiviral T cell responses and promote virus persistence. We report here that the fast-replicating LCMV strain Docile triggers a massive expansion of the Treg population that directly correlates with the size of the virus inoculum and its tendency to establish a chronic, persistent infection. This Treg cell proliferation was greatly enhanced in IL-21R-/- mice and depletion of Treg cells partially rescued defective CD8+ T cell cytokine responses and improved viral clearance in some but not all organs. Notably, IL-21 inhibited Treg cell expansion in a cell intrinsic manner. Moreover, experimental augmentation of Treg cells driven by injection of IL-2/anti-IL-2 immune complexes drastically impaired the functionality of the antiviral T cell response and impeded virus clearance. As a consequence, mice became highly susceptible to chronic infection following exposure to low virus doses. These findings reveal virus-driven Treg cell proliferation as potential evasion strategy that facilitates T cell exhaustion and virus persistence. Furthermore, they suggest that besides its primary function as a direct survival signal for antiviral CD8+ T cells during chronic infections, IL-21 may also indirectly promote CD8+ T cell poly-functionality by restricting the suppressive activity of infection-induced Treg cells.
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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.