ArticleJournal of immunology (Baltimore, Md. : 1950)2017
The Effect of Inhibitory Signals on the Priming of Drug Hapten-Specific T Cells That Express Distinct Vβ Receptors.
Article in Journal of immunology (Baltimore, Md. : 1950), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers, 1 of them a synthesis that pooled it.
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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- In Vitro Monitoring of Human T Cell Responses to Skin Sensitizing Chemicals-A Systematic Review.Cells · 2021Pooled it
- Immune checkpoint blockade lowers the threshold of naïve T-cell priming to drug-associated antigens in a dose-dependent fashion.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Immunological Drug-Drug Interactions Affect the Efficacy and Safety of Immune Checkpoint Inhibitor Therapies.Chemical research in toxicology · 2024Review
- Drug hypersensitivity reactions: review of the state of the science for prediction and diagnosis.Toxicological sciences : an official journal of the Society of Toxicology · 2024Review
- Protein Haptenation and Its Role in Allergy.Chemical research in toxicology · 2024Review
- A blinded in vitro analysis of the intrinsic immunogenicity of hepatotoxic drugs: implications for preclinical risk assessment.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Updates on the immunopathology and genomics of severe cutaneous adverse drug reactions.The Journal of allergy and clinical immunology · 2023Review
- Identifying Patients at Risk of Acute Kidney Injury among Patients Receiving Immune Checkpoint Inhibitors: A Machine Learning Approach.Diagnostics (Basel, Switzerland) · 2022Article
- Practical Implementation of Genetics: New Concepts in Immunogenomics to Predict, Prevent, and Diagnose Drug Hypersensitivity.The journal of allergy and clinical immunology. In practice · 2022Article
- Checkpoint Inhibition Reduces the Threshold for Drug-Specific T-Cell Priming and Increases the Incidence of Sulfasalazine Hypersensitivity.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Immunopharmacogenomics: Mechanisms of HLA-Associated Drug Reactions.Clinical pharmacology and therapeutics · 2021Review
- Incidence and risk factors of acute kidney injury, and its effect on mortality among Japanese patients receiving immune check point inhibitors: a single-center observational study.Clinical and experimental nephrology · 2021Observational
- Genomic Risk Factors Driving Immune-Mediated Delayed Drug Hypersensitivity Reactions.Frontiers in genetics · 2021Review
- Review
- The Roles of Immunoregulatory Networks in Severe Drug Hypersensitivity.Frontiers in immunology · 2021Review
- Drug and Chemical Allergy: A Role for a Specific Naive T-Cell Repertoire?Frontiers in immunology · 2021Review
- Balancing Cancer Immunotherapy Efficacy and Toxicity.The journal of allergy and clinical immunology. In practice · 2020Review
- Incidence and Clinical Features of Immune-Related Acute Kidney Injury in Patients Receiving Programmed Cell Death Ligand-1 Inhibitors.Kidney international reports · 2020Article
- Evolving insights into the mechanisms of toxicity associated with immune checkpoint inhibitor therapy.British journal of clinical pharmacology · 2020Review
- Application of hepatocyte-like cells to enhance hepatic safety risk assessment in drug discovery.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Review
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
Drug hypersensitivity involves the activation of T cells in an HLA allele-restricted manner. Because the majority of individuals who carry HLA risk alleles do not develop hypersensitivity, other parameters must control development of the drug-specific T cell response. Thus, we have used a T cell-priming assay and nitroso sulfamethoxazole (SMX-NO) as a model Ag to investigate the activation of specific TCR Vβ subtypes, the impact of programmed death -1 (PD-1), CTL-associated protein 4 (CTLA4), and T cell Ig and mucin domain protein-3 (TIM-3) coinhibitory signaling on activation of naive and memory T cells, and the ability of regulatory T cells (Tregs) to prevent responses. An expansion of the TCR repertoire was observed for nine Vβ subtypes, whereas spectratyping revealed that SMX-NO-specific T cell responses are controlled by public TCRs present in all individuals alongside private TCR repertoires specific to each individual. We proceeded to evaluate the extent to which the activation of these TCR Vβ-restricted Ag-specific T cell responses is governed by regulatory signals. Blockade of PD-L1/CTLA4 signaling dampened activation of SMX-NO-specific naive and memory T cells, whereas blockade of TIM-3 produced no effect. Programmed death-1, CTLA4, and TIM-3 displayed discrete expression profiles during drug-induced T cell activation, and expression of each receptor was enhanced on dividing T cells. Because these receptors are also expressed on Tregs, Treg-mediated suppression of SMX-NO-induced T cell activation was investigated. Tregs significantly dampened the priming of T cells. In conclusion, our findings demonstrate that distinct TCR Vβ subtypes, dysregulation of coinhibitory signaling pathways, and dysfunctional Tregs may influence predisposition to hypersensitivity.
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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.