ArticleThe Journal of experimental medicine1996
Interleukin-10 induces a long-term antigen-specific anergic state in human CD4+ T cells.
Article in The Journal of experimental medicine, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 212 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
212 citing papers in PubMed, 1 synthesis or guideline pooled it, 773 citations in OpenAlex.
- IL-10 promoter polymorphism associated with decreased risk of aGvHD after stem cell transplantation: a meta-analysis.International journal of hematology · 2013Pooled it
- Immunization of NSCLC patients with antigen-pulsed immature autologous dendritic cells.Lung cancer (Amsterdam, Netherlands) · 2007Trial
- Cytokine changes during interferon-beta therapy in multiple sclerosis: correlations with interferon dose and MRI response.Journal of neuroimmunology · 2007Trial
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- Efficacy of Local and Whole-Body Phototherapy for the Treatment of Various Types of Alopecia Areata.Photodermatology, photoimmunology & photomedicine · 2026Article
- Multiple sclerosis: molecular pathogenesis and therapeutic intervention.Signal transduction and targeted therapy · 2025Review
- Extracorporeal Photopheresis: Secreted Factors That Promote Immunomodulation.Transplantation direct · 2025Article
- Advances in interleukin-10-based therapies for pulmonary diseases: focus on targeted lung delivery systems.Frontiers in immunology · 2025Review
- Review
- Therapeutic induction of antigen-specific immune tolerance.Nature reviews. Immunology · 2024Review
- Role of Regulatory T Cells and Their Potential Therapeutic Applications in Celiac Disease.International journal of molecular sciences · 2023Review
- Intestinal Tr1 Cells Confer Protection against Colitis in the Absence of Foxp3+ Regulatory T Cell-Derived IL-10.ImmunoHorizons · 2023Article
- CD4Frontiers in immunology · 2023Review
- Impact of immune tolerance mechanisms on the efficacy of immunotherapy in primary and secondary liver cancers.Translational gastroenterology and hepatology · 2023Review
- Under the influence: environmental factors as modulators of neuroinflammation through the IL-10/IL-10R axis.Frontiers in immunology · 2023Review
- Article
- Cytokine storm and targeted therapy in hemophagocytic lymphohistiocytosis.Immunologic research · 2022Review
- Review
- Vitamin D, exercise, and immune health in athletes: A narrative review.Frontiers in immunology · 2022Review
- Psychological stress creates an immune suppressive environment in the lung that increases susceptibility of aged mice toFrontiers in cellular and infection microbiology · 2022Article
152 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Human CD4+ T cells, activated by allogeneic monocytes in a primary mixed lymphocyte reaction in the presence of exogenous interleukin (IL) 10, specifically failed to proliferate after restimulation with the same alloantigens. A comparable state of T cell unresponsiveness could be induced by activation of CD4+ T cells by cross-linked anti-CD3 monoclonal antibodies (mAbs) in the presence of exogenous IL-10. The anergic T cells failed to produce IL-2, IL-5, IL-10, interferon gamma, tumor necrosis factor alpha, and granulocyte/macrophage colony-stimulating factor. The IL-10-induced anergic state was long-lasting. T cell anergy could not be reversed after restimulation of the cells with anti-CD3 and anti-CD28 mAbs, although CD3 and CD28 expression was normal. In addition, restimulation of anergized T cells with anti-CD3 mAbs induced normal Ca2+ fluxes and resulted in increased CD3, CD28, and class II major histocompatibility complex expression, indicating that calcineurin-mediated signaling occurs in these anergic cells. However, the expression of the IL-2 receptor alpha chain was not upregulated, which may account for the failure of exogenous IL-2 to reverse the anergic state. Interestingly, anergic T cells and their nonanergic counterparts showed comparable levels of proliferation and cytokine production after activation with phorbol myristate acetate and Ca2+ ionophore, indicating that a direct activation of a protein kinase C-dependent pathway can overcome the tolerizing effect of IL-10. Taken together, these data demonstrate that IL-10 induces T cell anergy and therefore may play an important role in the induction and maintenance of antigen-specific T cell tolerance.
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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.