ArticleCell reports2016
Programmed Death-1 Culls Peripheral Accumulation of High-Affinity Autoreactive CD4 T Cells to Protect against Autoimmunity.
Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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Who cites it
32 citing papers in PubMed.
- PD-1+CD8+ T cells are clonally expanding effectors in human chronic inflammation.The Journal of clinical investigation · 2018Trial
- Immunotherapy in acute myeloid leukemia: The antibodies, TriKEs, and CARs on the arduous road to cure.Blood reviews · 2026Review
- Cytokine-induced PD-L1 and PD-L2 expression is preserved but reverse signalling is altered in rheumatoid arthritis fibroblast-like synoviocytes.Arthritis research & therapy · 2026Article
- Immune context governs stage-specific responses to depleting anti-PD-1 antibody in type 1 diabetes.Cell biomaterials · 2026Article
- 3-in-oneiScience · 2025Article
- Fat-to-blood recirculation of partially dysfunctional PD-1iScience · 2024Article
- Long-term outcomes and immune profiling in children with multisystem inflammatory syndrome (MIS-C).Acta bio-medica : Atenei Parmensis · 2023Article
- Novel immunoprofiling method for diagnosing SLE and evaluating therapeutic response.Lupus science & medicine · 2022Article
- Pembrolizumab and decitabine for refractory or relapsed acute myeloid leukemia.Journal for immunotherapy of cancer · 2022Article
- Folate Receptor 4-Expressing T cell Is Associated with Disease-Free Survival in Patients with Esophageal Squamous Cell Carcinoma.Disease markers · 2022Article
- Cytokine Release Syndrome in Cancer Patients Receiving Immune Checkpoint Inhibitors: A Case Series of 25 Patients and Review of the Literature.Frontiers in immunology · 2022Review
- Exploring the Pathogenic Role and Therapeutic Implications of Interleukin 2 in Autoimmune Hepatitis.Digestive diseases and sciences · 2021Review
- The Role of Programmed Death-1 in Type 1 Diabetes.Current diabetes reports · 2021Review
- The PD-1:PD-L1 axis in Inflammatory Arthritis.BMC rheumatology · 2021Review
- Immune Checkpoints, a Novel Class of Therapeutic Targets for Autoimmune Diseases.Frontiers in immunology · 2021Review
- PD-1 and PD-L1 Expression on Circulating Lymphocytes as a Marker of Epstein-Barr Virus Reactivation-Associated Proliferative Glomerulonephritis.International journal of molecular sciences · 2020Article
- Role of the PD-1/PD-L1 Dyad in the Maintenance of Pancreatic Immune Tolerance for Prevention of Type 1 Diabetes.Frontiers in endocrinology · 2020Review
- Analysis of Blimp-1 and PD-1/PD-L1 Immune Checkpoint in an Autoimmune Thyroiditis Animal Model.International journal of endocrinology · 2020Article
- Opposing peripheral fates of tissue-restricted self antigen-specific conventional and regulatory CD4European journal of immunology · 2020Article
- Examining pathogenic concepts of autoimmune hepatitis for cues to future investigations and interventions.World journal of gastroenterology · 2019Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Self-reactive CD4 T cells are incompletely deleted during thymic development, and their peripheral seeding highlights the need for additional safeguards to avert autoimmunity. Here, we show an essential role for the coinhibitory molecule programmed death-1 (PD-1) in silencing the activation of high-affinity autoreactive CD4 T cells. Each wave of self-reactive CD4 T cells that escapes thymic deletion autonomously upregulates PD-1 to maintain self-tolerance. By tracking the progeny derived from individual autoreactive CD4 T cell clones, we demonstrate that self-reactive cells with the greatest autoimmune threat and highest self-antigen affinity express the most PD-1. Reciprocally, PD-1 deprivation unleashes high-affinity self-reactive CD4 T cells in target tissues to exacerbate neuronal inflammation and autoimmune diabetes. Reliance on PD-1 to actively maintain self-tolerance may explain why exploiting this pathway by cancerous cells and invasive microbes efficiently subverts protective immunity, and why autoimmune side effects can develop after PD-1-neutralizing checkpoint therapies.
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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.