ArticleImmunology and cell biology2013
CD134/CD137 dual costimulation-elicited IFN-γ maximizes effector T-cell function but limits Treg expansion.
Article in Immunology and cell biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Decoding TNF receptor superfamily control of CD4Cell communication and signaling : CCS · 2026Review
- Increased Sirtuin 6 Activity in Tumor Cells Can Prompt CD4-Positive T-Cell Differentiation Into Regulatory T Cells and Impede Immune Surveillance in the Microenvironment.World journal of oncology · 2025Article
- Abrogation and homeostatic restoration of IgE responses by a universal IgE allergy CTL vaccine-The three signal self/non-self/self (S/NS/S) theory.Immunology · 2024Article
- BGB-A445, a novel non-ligand-blocking agonistic anti-OX40 antibody, exhibits superior immune activation and antitumor effects in preclinical models.Frontiers of medicine · 2023Article
- Optimal CD8Nature communications · 2022Article
- Thalidomide with blockade of co-stimulatory molecules prolongs the survival of alloantigen-primed mice with cardiac allografts.BMC immunology · 2020Article
- Blockade of OX40/OX40L pathway combined with ethylene-carbodiimide-fixed donor splenocytes induces donor-specific allograft tolerance in presensitized recipients.Annals of translational medicine · 2020Article
- CD137 agonist induces gastric cancer cell apoptosis by enhancing the functions of CD8Cancer cell international · 2020Article
- Costimulation Induces CD4 T Cell Antitumor Immunity via an Innate-like Mechanism.Cell reports · 2019Article
- An Immunotherapeutic CD137 Agonist Releases Eomesodermin from ThPOK Repression in CD4 T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Interferon-γ Drives TCell · 2017Article
- Amelioration of Inflammatory Cytokines Mix Stimulation: A Pretreatment of CD137 Signaling Study on VSMC.Mediators of inflammation · 2017Article
- Cytokines and metabolic factors regulate tumoricidal T-cell function during cancer immunotherapy.Immunotherapy · 2017Review
- Are Regulatory T Cells Defective in Type 1 Diabetes and Can We Fix Them?Journal of immunology (Baltimore, Md. : 1950) · 2016Review
- Costimulation Endows Immunotherapeutic CD8 T Cells with IL-36 Responsiveness during Aerobic Glycolysis.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Tumor-Unrelated CD4 T Cell Help Augments CD134 plus CD137 Dual Costimulation Tumor Therapy.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- 4-1BB Agonists: Multi-Potent Potentiators of Tumor Immunity.Frontiers in oncology · 2015Review
- Natural Killer Cell Functional Activity After 4-1BB Costimulation.Inflammation · 2015Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
T-cell tolerance to tumor antigens represents a major hurdle in generating tumor immunity. Combined administration of agonistic monoclonal antibodies (mAbs) to the costimulatory receptors CD134 plus CD137 can program T-cells responding to tolerogenic antigen to undergo expansion, and effector T-cell differentiation, and also elicits tumor immunity. Nevertheless, CD134 and CD137 agonists can also engage inhibitory immune components. To understand how immune stimulatory versus inhibitory components are regulated during CD134 plus CD137 dual costimulation (DCo), the current study utilized a model where DCo programs T-cells encountering a highly tolerogenic self-antigen to undergo effector differentiation. IFN-γ was found to have a pivotal role in maximizing the function of effector T-cells, while simultaneously limiting the expansion of CD4(+)CD25(+)Foxp3(+) Tregs. In antigen-responding effector T-cells, IFN-γ operates via a direct cell-intrinsic mechanism to cooperate with IL-2 to program maximal expression of granzyme B. Simultaneously, IFN-γ limits expression of the IL-2 receptor alpha chain (CD25) and IL-2 signaling through a mechanism that does not involve T-bet-mediated repression of IL-2. IFN-γ also limited CD25 and Foxp3 expression on bystanding CD4(+)Foxp3(+) Tregs, and limited the potential of these Tregs to expand. These effects could not be explained by the ability of IFN-γ to limit IL-2 availability. Taken together, during DCo IFN-γ interacts with IL-2 through distinct mechanisms to program maximal expression of effector molecules in antigen-responding T-cells, while simultaneously limiting Treg expansion.
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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.