ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Exogenous OX40 stimulation during lymphocytic choriomeningitis virus infection impairs follicular Th cell differentiation and diverts CD4 T cells into the effector lineage by upregulating Blimp-1.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Follicular T helper cells shape the HCV-specific CD4+ T cell repertoire after virus elimination.The Journal of clinical investigation · 2020Trial
- Probiotics and their metabolite spermidine enhance IFN-γCell reports. Medicine · 2024Article
- PDIA3 orchestrates effector T cell program by serving as a chaperone to facilitate the non-canonical nuclear import of STAT1 and PKM2.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Th1-Biased Hepatitis C Virus-Specific Follicular T Helper-Like Cells Effectively Support B Cells After Antiviral Therapy.Frontiers in immunology · 2021Article
- Th1 responses in vivo require cell-specific provision of OX40L dictated by environmental cues.Nature communications · 2020Article
- Therapeutic strategies for the costimulatory molecule OX40 in T-cell-mediated immunity.Acta pharmaceutica Sinica. B · 2020Review
- HCV-specific CD4+ T cells of patients with acute and chronic HCV infection display high expression of TIGIT and other co-inhibitory molecules.Scientific reports · 2019Article
- OX40 (CD134) and OX40 ligand, important immune checkpoints in cancer.OncoTargets and therapy · 2019Article
- Correlates of Follicular Helper Bias in the CD4 T Cell Response to a Retroviral Antigen.Frontiers in immunology · 2018Article
- T Cell/B Cell Collaboration and Autoimmunity: An Intimate Relationship.Frontiers in immunology · 2018Review
- Determination of T Follicular Helper Cell Fate by Dendritic Cells.Frontiers in immunology · 2018Review
- Molecular Control of Follicular Helper T cell Development and Differentiation.Frontiers in immunology · 2018Review
- Signals that drive T follicular helper cell formation.Immunology · 2017Review
- Oncolytic VSV Primes Differential Responses to Immuno-oncology Therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- OX40, OX40L and Autoimmunity: a Comprehensive Review.Clinical reviews in allergy & immunology · 2016Review
- Review
- Regulators of Tfh Cell Differentiation.Frontiers in immunology · 2016Review
- Innate and Adaptive Immune Regulation During Chronic Viral Infections.Annual review of virology · 2015Review
- OX40 Ligand Contributes to Human Lupus Pathogenesis by Promoting T Follicular Helper Response.Immunity · 2015Article
- The regulation of T follicular helper responses during infection.Current opinion in immunology · 2015Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
T cell costimulation is a key component of adaptive immunity to viral infection but has also been associated with pathology because of excessive or altered T cell activity. We recently demonstrated that the TNFR family costimulatory molecule OX40 (CD134) is critically required to sustain antiviral T cell and Ab responses that enable control of viral replication in the context of chronic lymphocytic choriomeningitis virus (LCMV) infection. In this study, we investigated whether reinforcing OX40 stimulation through an agonist Ab had the potential to prevent LCMV persistence. We observed that anti-OX40 injection early after LCMV clone 13 infection increased CD8 T cell-mediated immunopathology. More strikingly, OX40 stimulation of virus-specific CD4 T cells promoted expression of the transcriptional repressor Blimp-1 and diverted the majority of cells away from follicular Th cell differentiation. This occurred in both acute and chronic infections, and resulted in dramatic reductions in germinal center and Ab responses to the viral infection. The effect of the OX40 agonist was dependent on IL-2 signaling and the timing of OX40 stimulation. Collectively, our data demonstrate that excessive OX40 signaling can result in deleterious consequences in the setting of LCMV infection.
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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.