ArticleGlia2014
Glial cells suppress postencephalitic CD8+ T lymphocytes through PD-L1.
Article in Glia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 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
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Potential beneficial effects of PD-1/PD-L1 blockade in Alzheimer's disease: a systematic review and meta-analysis of preclinical and clinical studies.Molecular psychiatry · 2026Pooled it
- The Impact of Antigen Presentation on BBB Disruption and Neuroinflammation.Physiology (Bethesda, Md.) · 2026Review
- Astrocyte-driven immunosuppression in the brain tumor microenvironment.Nature immunology · 2026Review
- Persistent microglial activation following neonatal CMV infection mediates neurodegeneration.Science advances · 2026Article
- Targeting immunosuppressive network in glioblastoma: Emerging strategies to overcome immunodeficiency and enhance therapeutic efficacy.Acta pharmaceutica Sinica. B · 2026Review
- Microglial PD-1/PD-L1 axis in CNS demyelinating diseases: a dual immunoregulatory perspective.Frontiers in cellular neuroscience · 2026Review
- Divergent Crosstalk Between Microglia and T Cells in Brain Cancers: Implications for Novel Therapeutic Strategies.Biomedicines · 2025Review
- Programmed Cell Death Protein 1 Contributes to Oral Cancer Pain via Regulating Tumor Necrosis Factor Alpha in the Spinal Trigeminal Nucleus Caudalis.Current neuropharmacology · 2025Article
- Deciphering T Cell Dynamics in Alzheimer's Disease Pathogenesis: Insights and Implications.Current neuropharmacology · 2025Review
- The role of inhibitory immune checkpoint receptors in the pathogenesis of Alzheimer's disease.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Immune responses drive chorioretinitis and retinal pathology after neonatal CMV infection.Science advances · 2024Article
- Differential Effects of Extracellular Vesicles from Two Different Glioblastomas on Normal Human Brain Cells.Neurology international · 2024Article
- Limitations and potential strategies of immune checkpoint blockade in age-related neurodegenerative disorders.The journal of physiological sciences : JPS · 2024Review
- Age-dependent Powassan virus lethality is linked to glial cell activation and divergent neuroinflammatory cytokine responses in a murine model.Journal of virology · 2024Article
- CD8CNS neuroscience & therapeutics · 2024Article
- Retroviral b-Zip protein (HBZ) contributes to the release of soluble and exosomal immune checkpoint molecules in the context of neuroinflammation.Journal of extracellular biology · 2023Article
- Transcriptomic Profiling Identifies CD8Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Tumor Immune Microenvironment of Brain Metastases: Toward Unlocking Antitumor Immunity.Cancer discovery · 2022Review
- Programmed Death-1 Deficiency Aggravates Motor Dysfunction in MPTP Model of Parkinson's Disease by Inducing Microglial Activation and Neuroinflammation in Mice.Molecular neurobiology · 2022Article
- Expression, prognostic significance and therapeutic implications of PD-L1 in gliomas.Neuropathology and applied neurobiology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Engagement of the programmed death (PD)-1 receptor on activated cells by its ligand (PD-L1) is a mechanism for suppression of activated T-lymphocytes. Microglia, the resident inflammatory cells of the brain, are important for pathogen detection and initiation of innate immunity, however, a novel role for these cells as immune regulators has also emerged. PD-L1 on microglia has been shown to negatively regulate T-cell activation in models of multiple sclerosis and acute viral encephalitis. In this study, we investigated the role of glial cell PD-L1 in controlling encephalitogenic CD8(+) T-lymphocytes, which infiltrate the brain to manage viral infection, but remain to produce chronic neuroinflammation. Using a model of chronic neuroinflammation following murine cytomegalovirus (MCMV)-induced encephalitis, we found that CD8(+) T-cells persisting within the brain expressed PD-1. Conversely, activated microglia expressed PD-L1. In vitro, primary murine microglia, which express low basal levels of PD-L1, upregulated the co-inhibitory ligand on IFN-γ-treatment. Blockade of the PD-1: PD-L1 pathway in microglial: CD8(+) T-cell co-cultures increased T-cell IFN-γ and interleukin (IL)-2 production. We observed a similar phenomenon following blockade of this co-inhibitory pathway in astrocyte: CD8(+) T-cell co-cultures. Using ex vivo cultures of brain leukocytes, including microglia and CD8(+) T-cells, obtained from mice with MCMV-induced chronic neuroinflammation, we found that neutralization of either PD-1 or PD-L1 increased IFN-γ production from virus-specific CD8(+) T-cells stimulated with MCMV IE1168-176 peptide. These data demonstrate that microglia and astrocytes control antiviral T-cell responses and suggest a therapeutic potential of PD1: PD-L1 modulation to manage the deleterious consequences of uncontrolled neuroinflammation.
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What OpenQuestion holds
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.