ArticleThe Journal of experimental medicine2012
Programmed death 1 protects from fatal circulatory failure during systemic virus infection of mice.
Article in The Journal of experimental medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers, 2 of them syntheses 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
147 citing papers in PubMed, 2 syntheses or guidelines pooled it, 202 citations in OpenAlex.
- Comprehensive adjusted outcome data are needed to assess the impact of immune checkpoint inhibitors in cancer patients with COVID-19: Results of a systematic review and meta-analysis.Reviews in medical virology · 2022Pooled it
- Anti-PD-L1 Therapy Does Not Improve Survival in a Murine Model of Lethal Staphylococcus aureus Pneumonia.The Journal of infectious diseases · 2021Pooled it
- Exacerbation of CMV and Nontuberculous Mycobacterial Infections Following PD-1 Blockade for HIV-Associated Kaposi Sarcoma.Open forum infectious diseases · 2024Trial
- Investigating CD8 T Cell Exhaustion in Chronic LCMV Infection by Flow Cytometry.Current protocols · 2026Article
- Humanized Anti-PD-1 Antibodies Generated Using The Conditional Kernel-Elastic Autoencoder.bioRxiv : the preprint server for biology · 2026Article
- PD-1⁺ CD8⁺ T cells: roles of PD-1 beyond an exhaustion marker.Seminars in immunopathology · 2026Review
- T cells in acute and chronic myocarditis: from diagnosis to treatment.European heart journal · 2026Review
- Efficacy of Immune Checkpoint Inhibitors and Oncoviruses in Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- TLR7-mediated inflammation drives PD-L1 upregulation and T cell exhaustion during influenza A virus infection.iScience · 2026Article
- Ocular manifestations and immunological profiles of thyroid eye disease with lacrimal gland enlargement.Frontiers in endocrinology · 2026Article
- Memory-like CD8Frontiers in immunology · 2026Article
- Lpar5 regulates the CD8 T-cell response to persistent virus infection by altering exhaustion programming, survival, and NK receptor expression.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- CD8 T cells mediate immunosurveillance for neoantigen+ epithelial stem cells in the colon.bioRxiv : the preprint server for biology · 2025Article
- Nanomedicine targeting the PD-1/PD-L1 axis in autoimmune diseases: breaking conventional barriers to restore immune tolerance.Journal of nanobiotechnology · 2025Review
- Selective expansion of TCF7-expressing tumor-reactive T cell subpopulations during ovarian tumor-infiltrating T cell production ex vivo.Science China. Life sciences · 2025Article
- Lymph nodes fuel KLF2-dependent effector CD8Nature immunology · 2025Article
- Angiogenic CD8 T cells from PWH induce Granzymes-dependent PAR1 activation promoting endothelial inflammation.bioRxiv : the preprint server for biology · 2025Article
- BCOR and ZC3H12A suppress a core stemness program in exhausted CD8+ T cells.The Journal of experimental medicine · 2025Article
- The PD-1/PD-L1 pathway and Epstein-Barr virus.European journal of medical research · 2025Review
- One Step Ahead: Preventing Tumor Adaptation to Immune Therapy.American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting · 2025Review
87 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The inhibitory programmed death 1 (PD-1)-programmed death ligand 1 (PD-L1) pathway contributes to the functional down-regulation of T cell responses during persistent systemic and local virus infections. The blockade of PD-1-PD-L1-mediated inhibition is considered as a therapeutic approach to reinvigorate antiviral T cell responses. Yet previous studies reported that PD-L1-deficient mice develop fatal pathology during early systemic lymphocytic choriomeningitis virus (LCMV) infection, suggesting a host protective role of T cell down-regulation. As the exact mechanisms of pathology development remained unclear, we set out to delineate in detail the underlying pathogenesis. Mice deficient in PD-1-PD-L1 signaling or lacking PD-1 signaling in CD8 T cells succumbed to fatal CD8 T cell-mediated immunopathology early after systemic LCMV infection. In the absence of regulation via PD-1, CD8 T cells killed infected vascular endothelial cells via perforin-mediated cytolysis, thereby severely compromising vascular integrity. This resulted in systemic vascular leakage and a consequential collapse of the circulatory system. Our results indicate that the PD-1-PD-L1 pathway protects the vascular system from severe CD8 T cell-mediated damage during early systemic LCMV infection, highlighting a pivotal physiological role of T cell down-regulation and suggesting the potential development of immunopathological side effects when interfering with the PD-1-PD-L1 pathway during systemic virus infections.
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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.