ArticleThe Journal of experimental medicine2000
Coupling of peripheral tolerance to endogenous interleukin 10 promotes effective modulation of myelin-activated T cells and ameliorates experimental allergic encephalomyelitis.
Article in The Journal of experimental medicine, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 67 citations in OpenAlex.
- Interleukin-10 induces TNF-driven apoptosis and ROS production in salivary gland cancer cells.Heliyon · 2024Article
- Peripheral tolerance by Treg via constraining OX40 signal in autoreactive T cells against desmoglein 3, a target antigen in pemphigus.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Apoptotic cell-induced AhR activity is required for immunological tolerance and suppression of systemic lupus erythematosus in mice and humans.Nature immunology · 2018Article
- Antigen-Specific Immune Modulation Targets mTORC1 Function To Drive Chemokine Receptor-Mediated T Cell Tolerance.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- The neuroprotective effect exerted by oligodendroglial progenitors on ischemically impaired hippocampal cells.Molecular neurobiology · 2014Article
- Regulatory T-cell vaccination independent of auto-antigen.Experimental & molecular medicine · 2014Review
- In trans T cell tolerance exacerbates experimental allergic encephalomyelitis by interfering with protective antibody responses.Journal of neuroimmunology · 2014Article
- Article
- Antigen-specific effector CD4 T lymphocytes school lamina propria dendritic cells to transfer innate tolerance.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Antigen-specific tolerance in immunotherapy of Th2-associated allergic diseases.Critical reviews in immunology · 2013Review
- T cell dynamics during induction of tolerance and suppression of experimental allergic encephalomyelitis.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- FoxP3+RORgammat+ T helper intermediates display suppressive function against autoimmune diabetes.Journal of immunology (Baltimore, Md. : 1950) · 2010Article
- Cytokine switch and bystander suppression of autoimmune responses to multiple antigens in experimental autoimmune encephalomyelitis by a single recombinant T-cell receptor ligand.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2009Article
- Fetal exposure to high-avidity TCR ligand enhances expansion of peripheral T regulatory cells.Journal of immunology (Baltimore, Md. : 1950) · 2008Article
- Innocuous IFNgamma induced by adjuvant-free antigen restores normoglycemia in NOD mice through inhibition of IL-17 production.The Journal of experimental medicine · 2008Article
- Tolerance in the absence of autoantigen.Endocrine, metabolic & immune disorders drug targets · 2007Review
- Splenic Dendritic Cells from Antigen-Fed Mice Induced Antigen-Specific T Cell Unresponsiveness in vivo.Cytotechnology · 2003Article
- Article
- Tr1 cell-dependent active tolerance blunts the pathogenic effects of determinant spreading.The Journal of clinical investigation · 2002Article
- On the role of dendritic cells in peripheral T cell tolerance and modulation of autoimmunity.The Journal of experimental medicine · 2002Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Several immune-based approaches are being considered for modulation of inflammatory T cells and amelioration of autoimmune diseases. The most recent strategies include simulation of peripheral self-tolerance by injection of adjuvant free antigen, local delivery of cytokines by genetically altered T cells, and interference with the function of costimulatory molecules. Although promising results have been obtained from these studies that define mechanisms of T cell modulation, efficacy, practicality, and toxicity, concerns remain unsolved, thereby justifying further investigations to define alternatives for effective downregulation of aggressive T cells. In prior studies, we demonstrated that an immunoglobulin (Ig) chimera carrying the encephalitogenic proteolipid protein (PLP)1 peptide corresponding to amino acid sequence 139-151 of PLP, Ig-PLP1, is presented to T cells approximately 100-fold better than free PLP1. Here, we demonstrate that aggregation endows Ig-PLP1 with an additional feature, namely, induction of interleukin (IL)-10 production by macrophages and dendritic cells, both of which are antigen-presenting cells (APCs). These functions synergize in vivo and drive effective modulation of autoimmunity. Indeed, it is shown that animals with ongoing active experimental allergic encephalomyelitis dramatically reduce the severity of their paralysis when treated with adjuvant free aggregated Ig-PLP1. Moreover, IL-10 displays bystander antagonism on unrelated autoreactive T cells, allowing for reversal of disease involving multiple epitopes. Therefore, aggregated Ig-PLP1 likely brings together a peripheral T cell tolerance mechanism emanating from peptide presentation by APCs expressing suboptimal costimulatory molecules and IL-10 bystander suppression to drive a dual-modal T cell modulation system effective for reversal of autoimmunity involving several epitopes and diverse T cell specificities.
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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.