ArticleJournal of immunology (Baltimore, Md. : 1950)2016
NADPH Oxidase-Derived Superoxide Provides a Third Signal for CD4 T Cell Effector Responses.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 51 citations in OpenAlex.
- Metabolic Blockade of Glycolysis Diminishes Autoreactive CD4 T-Cell Effector Responses in Type 1 Diabetes.Diabetes · 2026Article
- Oxidative Stress, Post-Translational Modifications, and Type 1 Diabetes Pathogenesis.Immunological reviews · 2026Review
- Jieduquyuziyin prescription for systemic lupus erythematosus: a system-level therapeutic strategy for immunological recalibration.Chinese medicine · 2026Review
- Immunometabolism in systemic lupus erythematosus.Nature reviews. Rheumatology · 2025Review
- Enhanced ROS Production and Mitochondrial Metabolic Shifts in CD4International journal of molecular sciences · 2024Article
- Restoration of LAMP2A expression in old mice leads to changes in the T cell compartment that support improved immune function.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Gut redox and microbiome: charting the roadmap to T-cell regulation.Frontiers in immunology · 2024Review
- Immunoregulation: the interplay between metabolism and redox homeostasis.Frontiers in transplantation · 2023Review
- Role of reactive oxygen species and mitochondrial damage in rheumatoid arthritis and targeted drugs.Frontiers in immunology · 2023Review
- The Redox-Metabolic Couple of T Lymphocytes: Potential Consequences for Hypertension.Antioxidants & redox signaling · 2021Review
- Reactive Oxygen Species in Autoimmune Cells: Function, Differentiation, and Metabolism.Frontiers in immunology · 2021Review
- Article
- Reactive Oxygen Species: Do They Play a Role in Adaptive Immunity?Frontiers in immunology · 2021Review
- Targeting Mitochondrial-Derived Reactive Oxygen Species in T Cell-Mediated Autoimmune Diseases.Frontiers in immunology · 2021Review
- Metabolic Reprogramming and Reactive Oxygen Species in T Cell Immunity.Frontiers in immunology · 2021Review
- NOX2ko Mice Show Largely Increased Expression of a Mutated NOX2 mRNA Encoding an Inactive NOX2 Protein.Antioxidants (Basel, Switzerland) · 2020Article
- Localized Immunosuppression With Tannic Acid Encapsulation Delays Islet Allograft and Autoimmune-Mediated Rejection.Diabetes · 2020Article
- A small molecule G6PD inhibitor reveals immune dependence on pentose phosphate pathway.Nature chemical biology · 2020Article
- Signaling Response to Transient Redox Stress in Human Isolated T Cells: Molecular Sensor Role of Syk Kinase and Functional Involvement of IL2 Receptor and L-Selectine.Sensors (Basel, Switzerland) · 2020Article
- The Influence of Reactive Oxygen Species in the Immune System and Pathogenesis of Multiple Sclerosis.Autoimmune diseases · 2020Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Originally recognized for their direct induced toxicity as a component of the innate immune response, reactive oxygen species (ROS) can profoundly modulate T cell adaptive immune responses. Efficient T cell activation requires: signal 1, consisting of an antigenic peptide-MHC complex binding with the TCR; signal 2, the interaction of costimulatory molecules on T cells and APCs; and signal 3, the generation of innate immune-derived ROS and proinflammatory cytokines. This third signal, in particular, has proven essential in generating productive and long-lasting immune responses. Our laboratory previously demonstrated profound Ag-specific hyporesponsiveness in the absence of NADPH oxidase-derived superoxide. To further examine the consequences of ROS deficiency on Ag-specific T cell responses, our laboratory generated the OT-II.Ncf1(m1J) mouse, possessing superoxide-deficient T cells recognizing the nominal Ag OVA323-339 In this study, we demonstrate that OT-II.Ncf1(m1J) CD4 T cells displayed a severe reduction in Th1 T cell responses, in addition to blunted IL-12R expression and severely attenuated proinflammatory chemokine ligands. Conversely, IFN-γ synthesis and IL-12R synthesis were rescued by the addition of exogenous superoxide via the paramagnetic superoxide donor potassium dioxide or superoxide-sufficient dendritic cells. Ultimately, these data highlight the importance of NADPH oxidase-derived ROS in providing a third signal for adaptive immune maturation by modulating the IL-12/IL-12R pathway and the novelty of the OT-II.Ncf1(m1J) mouse model to determine the role of redox-dependent signaling on effector responses. Thus, targeting ROS represents a promising therapeutic strategy in dampening Ag-specific T cell responses and T cell-mediated autoimmune diseases, such as type 1 diabetes.
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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.