ArticleThe Journal of experimental medicine1999
Interleukin 12 protects from a T helper type 1-mediated autoimmune disease, experimental autoimmune uveitis, through a mechanism involving interferon gamma, nitric oxide, and apoptosis.
Article in The Journal of experimental medicine, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 206 citations in OpenAlex.
- Th17 Response in Uveitis: A Double-Edged Sword in Ocular Inflammation and Immune Regulation.Clinical reviews in allergy & immunology · 2025Review
- Inflammatory cytokines as mediators of retinal endothelial barrier dysfunction in non-infectious uveitis.Clinical & translational immunology · 2023Review
- Uveitis: Molecular Pathogenesis and Emerging Therapies.Frontiers in immunology · 2021Review
- Autoimmunity to neuroretina in the concurrent absence of IFN-γ and IL-17A is mediated by a GM-CSF-driven eosinophilic inflammation.Journal of autoimmunity · 2020Article
- Viewing Autoimmune Pathogenesis from the Perspective of Antigen Processing and Determinant Hierarchy.Critical reviews in immunology · 2020Article
- Article
- IFNγ: signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy.Nature reviews. Immunology · 2018Review
- Review
- Inhibition of T cell-mediated inflammation in uveitis by a novel anti-CD3 antibody.Arthritis research & therapy · 2017Article
- Serum Th1 and Th17 related cytokines and autoantibodies in patients with Posner-Schlossman syndrome.PloS one · 2017Article
- Similarities in the Metabolic Reprogramming of Immune System and Endothelium.Frontiers in immunology · 2017Review
- Chronic exposure to trichloroethylene increases DNA methylation of the Ifng promoter in CD4Toxicology letters · 2016Article
- Synergistic COX2 Induction by IFNγ and TNFα Self-Limits Type-1 Immunity in the Human Tumor Microenvironment.Cancer immunology research · 2016Article
- NK-DC crosstalk controls the autopathogenic Th17 response through an innate IFN-γ-IL-27 axis.The Journal of experimental medicine · 2015Article
- Galectin-9 induced myeloid suppressor cells expand regulatory T cells in an IL-10-dependent manner in CVB3-induced acute myocarditis.International journal of molecular sciences · 2014Article
- Interleukin-12 (IL-12p70) Promotes Induction of Highly Potent Th1-Like CD4(+)CD25(+) T Regulatory Cells That Inhibit Allograft Rejection in Unmodified Recipients.Frontiers in immunology · 2014Article
- TNF-α and IFN-γ gene variation and genetic susceptibility to type 1 diabetes and its microangiopathic complications.Journal of diabetes and metabolic disorders · 2014Article
- Abrogation of Rbpj attenuates experimental autoimmune uveoretinitis by inhibiting IL-22-producing CD4+ T cells.PloS one · 2014Article
- Hyperperfusion in progressive multifocal leukoencephalopathy is associated with disease progression and absence of immune reconstitution inflammatory syndrome.Brain : a journal of neurology · 2013Article
- Nitrosothiols in the immune system: signaling and protection.Antioxidants & redox signaling · 2013Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Pathogenic effector T cells in experimental autoimmune uveitis (EAU) are T helper type 1-like, and interleukin (IL)-12 is required for their generation and function. Therefore, we expected that IL-12 administration would have disease-enhancing effects. Mice were immunized with a uveitogenic regimen of the retinal antigen interphotoreceptor retinoid-binding protein, treated with IL-12 (100 ng/d for 5 d), and EAU was assessed by histopathology. Unexpectedly, IL-12 treatment failed to enhance EAU in resistant strains and downregulated disease in susceptible strains. Only treatment during the first, but not during the second, week after immunization was consistently protective. High levels of interferon gamma (IFN-gamma) were present in the serum during IL-12 treatment, but subsequent antigen-specific IFN-gamma production in protected mice was diminished, as were IL-5 production, lymph node cell proliferation, and serum antibody levels. Treated mice had fewer cells and evidence of enhanced apoptosis in the draining lymph nodes. Unlike wild-type mice, IFN-gamma-deficient, inducible nitric oxide synthase (iNOS)-deficient, and Bcl-2(lck) transgenic mice were poorly protected by IL-12, whereas IL-10-deficient mice were protected. We conclude that administration of IL-12 aborts disease by curtailing development of uveitogenic effector T cells. The data are compatible with the interpretation that IL-12 induces systemic hyperinduction of IFN-gamma, causing activation of iNOS and production of NO, which mediates protection at least in part by triggering Bcl-2 regulated apoptotic deletion of the antigen-specific T cells as they are being primed.
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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.