ArticleJournal of immunology (Baltimore, Md. : 1950)2012
New insights on OX40 in the control of T cell immunity and immune tolerance in vivo.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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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
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Who cites it
58 citing papers in PubMed, 100 citations in OpenAlex.
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- Decoding TNF receptor superfamily control of CD4Cell communication and signaling : CCS · 2026Review
- Transcription factor Etv3 controls the tolerogenic function of dendritic cells.Science (New York, N.Y.) · 2026Article
- TSLP promotes GATA3-expressing effector regulatory T cells via DC2 derived from transitional DCs.Nature immunology · 2026Article
- Prognostic value of the co-stimulatory molecule OX40 expression in Extranodal Natural Killer/T-cell Lymphoma.Annals of medicine · 2025Article
- Generating tolerance through in situ recruitment of regulatory T cells for allogeneic cell transplantation in a bioengineered lymphoid platform.Materials today. Bio · 2025Article
- TNF superfamily molecules in atherosclerosis: mechanistic insights and therapeutic translation.Frontiers in immunology · 2025Review
- The homeostasis and heterogeneity of regulatory T cells in sepsis.Burns & trauma · 2025Article
- IFNγ Production by Functionally Reprogrammed Tregs Promotes Antitumor Efficacy of OX40/CD137 Bispecific Agonist Therapy.Cancer research communications · 2024Article
- Reprogramming of regulatory T cells in inflammatory tumor microenvironment: can it become immunotherapy turning point?Frontiers in immunology · 2024Review
- Ox40-Cre-mediated deletion of BRD4 reveals an unexpected phenotype of hair follicle stem cells in alopecia.JCI insight · 2022Article
- The Implementation of TNFRSF Co-Stimulatory Domains in CAR-T Cells for Optimal Functional Activity.Cancers · 2022Review
- Critical Roles of Balanced T Helper 9 Cells and Regulatory T Cells in Allergic Airway Inflammation and Tumor Immunity.Journal of immunology research · 2021Review
- Harnessing the Complete Repertoire of Conventional Dendritic Cell Functions for Cancer Immunotherapy.Pharmaceutics · 2020Review
- The promise of CD4Haematologica · 2019Review
- Immunologic Features of Patients With Advanced Hepatocellular Carcinoma Before and During Sorafenib or Anti-programmed Death-1/Programmed Death-L1 Treatment.Clinical and translational gastroenterology · 2019Article
- Association of OX40 gene polymorphisms (rs17568G/A and rs229811A/C) with head and neck squamous cell carcinoma.Molecular biology reports · 2019Article
- Costimulation Induces CD4 T Cell Antitumor Immunity via an Innate-like Mechanism.Cell reports · 2019Article
- Critical role of OX40 signaling in the TCR-independent phase of human and murine thymic Treg generation.Cellular & molecular immunology · 2019Article
- Molecular Mechanisms Controlling Foxp3 Expression in Health and Autoimmunity: From Epigenetic to Post-translational Regulation.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
OX40 is a T cell costimulatory molecule that belongs to the TNFR superfamily. In the absence of immune activation, OX40 is selectively expressed by Foxp3(+) regulatory T cells (Tregs), but not by resting conventional T cells. The exact role of OX40 in Treg homeostasis and function remains incompletely defined. In this study, we demonstrate that OX40 engagement in vivo in naive mice induces initial expansion of Foxp3(+) Tregs, but the expanded Tregs have poor suppressive function and exhibit features of exhaustion. We also show that OX40 enables the activation of the Akt and Stat5 pathways in Tregs, resulting in transient proliferation of Tregs and reduced levels of Foxp3 expression. This creates a state of relative IL-2 deficiency in naive mice that further impacts Tregs. This exhausted Treg phenotype can be prevented by exogenous IL-2, as both OX40 and IL-2 agonists drive further expansion of Tregs in vivo. Importantly, Tregs expanded by both OX40 and IL-2 agonists are potent suppressor cells, and in a heart transplant model, they promote long-term allograft survival. Our data reveal a novel role for OX40 in promoting immune tolerance and may have important clinical implications.
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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.