ArticlePloS one2014
Perforin competent CD8 T cells are sufficient to cause immune-mediated blood-brain barrier disruption.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
- The Impact of Antigen Presentation on BBB Disruption and Neuroinflammation.Physiology (Bethesda, Md.) · 2026Review
- TMEM119+ microglia MHC class I restricted antigen presentation impacts CD8 T cell memory, effector status, and blood-brain barrier disruption during neurotropic virus infection.Research square · 2026Article
- CD11c+ CD8 T cells cause IFN-γ-dependent autoimmune neuroinflammation that is restrained by PD-1 signaling.JCI insight · 2026Article
- Review
- Targeted Drug Delivery in Animal Models of Demyelination: The Role of Plant-Based Nanoparticles with a Focus on Multiple Sclerosis.Molecular neurobiology · 2026Review
- Heightened effector immune cell infiltration of the hippocampus concurrently with brain ventricular volume expansion in aged APP/PS1 mice.Journal of neuroimmunology · 2025Article
- Astrocytic RIPK3 exerts protective anti-inflammatory activity in mice with viral encephalitis by transcriptional induction of serpins.Science signaling · 2025Article
- CD8 T cells as drivers of blood-brain barrier disruption.Trends in neurosciences · 2025Review
- A case report and mini-review of Crimean-Congo hemorrhagic fever with encephalitis: an unexpected complication.Journal of neurovirology · 2025Review
- Single-cell sequencing reveals intracranial microvasculature-derived CXCL12 promotes CD8Journal of neuroinflammation · 2025Article
- Single-cell and spatiotemporal transcriptomic profiling of brain immune infiltration following Venezuelan equine encephalitis virus infection.Frontiers in immunology · 2024Article
- Article
- Assessment of Chimeric Antigen Receptor T Cell-Associated Toxicities Using an Acute Lymphoblastic Leukemia Patient-derived Xenograft Mouse Model.Journal of visualized experiments : JoVE · 2023Article
- Mice lacking perforin have improved regeneration of the injured femoral nerve.Neural regeneration research · 2022Article
- The Potential Role of COVID-19 in the Pathogenesis of Multiple Sclerosis-A Preliminary Report.Viruses · 2021Review
- Resolvin D3 Promotes Inflammatory Resolution, Neuroprotection, and Functional Recovery After Spinal Cord Injury.Molecular neurobiology · 2021Article
- Targeting of Perforin Inhibitor into the Brain Parenchyma Via a Prodrug Approach Can Decrease Oxidative Stress and Neuroinflammation and Improve Cell Survival.Molecular neurobiology · 2020Article
- Conditional Silencing of H-2DJournal of immunology (Baltimore, Md. : 1950) · 2020Article
- Facets of Theiler's Murine Encephalomyelitis Virus-Induced Diseases: An Update.International journal of molecular sciences · 2019Review
- The peripheral immune response after stroke-A double edge sword for blood-brain barrier integrity.CNS neuroscience & therapeutics · 2018Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Numerous neurological disorders are characterized by central nervous system (CNS) vascular permeability. However, the underlying contribution of inflammatory-derived factors leading to pathology associated with blood-brain barrier (BBB) disruption remains poorly understood. In order to address this, we developed an inducible model of BBB disruption using a variation of the Theiler's murine encephalomyelitis virus (TMEV) model of multiple sclerosis. This peptide induced fatal syndrome (PIFS) model is initiated by virus-specific CD8 T cells and results in severe CNS vascular permeability and death in the C57BL/6 mouse strain. While perforin is required for BBB disruption, the cellular source of perforin has remained unidentified. In addition to CD8 T cells, various innate immune cells also express perforin and therefore could also contribute to BBB disruption. To investigate this, we isolated the CD8 T cell as the sole perforin-expressing cell type in the PIFS model through adoptive transfer techniques. We determined that C57BL/6 perforin-/- mice reconstituted with perforin competent CD8 T cells and induced to undergo PIFS exhibited: 1) heightened CNS vascular permeability, 2) increased astrocyte activation as measured by GFAP expression, and 3) loss of linear organization of BBB tight junction proteins claudin-5 and occludin in areas of CNS vascular permeability when compared to mock-treated controls. These results are consistent with the characteristics associated with PIFS in perforin competent mice. Therefore, CD8 T cells are sufficient as a sole perforin-expressing cell type to cause BBB disruption in the PIFS model.
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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.