ArticleThe Journal of clinical investigation2023
CD8+ T cells recognizing a neuron-restricted antigen injure axons in a model of multiple sclerosis.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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.
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Who cites it
24 citing papers in PubMed, 21 citations in OpenAlex.
- The neuroimmune network in Alzheimer's and Parkinson's diseases: from mechanistic insights to biomarker-guided immunotherapies and clinical translation.Inflammopharmacology · 2026Review
- MIF-MAPMS: Enhancing identification of myelin autoantigenic peptides in multiple sclerosis through multimodal information fusion.Protein science : a publication of the Protein Society · 2026Article
- Article
- Human iPSC-derived neurons stimulated with IFNγ present HLA class I-restricted antigens to cytotoxic CD8Journal of neuroinflammation · 2026Article
- Mitochondrial dysfunction in neurodegenerative disorders: mechanisms and therapeutic advances.Molecular biomedicine · 2026Review
- Human neurons stimulated with IFNγ present HLA class I-restricted autoantigens to cytotoxic CD8bioRxiv : the preprint server for biology · 2026Article
- Elucidating the Causal Relationships Between B Cells, Dendritic Cells, and Multiple Sclerosis Pathogenesis.Brain and behavior · 2026Article
- Microbial-Immune Interplay in CNS Autoimmune Diseases: Lessons from Animal Models and Clinical Studies.European journal of immunology · 2026Review
- Proteasome 20S beta 8 (PSMB8) as a metabolic switcher of neuronal ferroptosis in multiple sclerosis.Cell death and differentiation · 2026Article
- Mechanisms of Epstein-Barr virus-associated autoimmunity: a comparative overview.Frontiers in immunology · 2026Review
- T cell-mediated immunodysregulation in multiple sclerosis: from pathogenic subsets to therapeutic advances.Frontiers in immunology · 2026Review
- Multi-omic spatially resolved analysis of the neuroinflammatory response to intracortical microelectrode arrays.Biomaterials · 2026Article
- A focus on the normal-appearing white and gray matter within the multiple sclerosis brain: a link to smoldering progression.Acta neuropathologica · 2025Review
- PSR-MAPMS: A new approach for the interpretable prediction of myelin autoantigenic peptides in multiple sclerosis using multi-source propensity scores.Protein science : a publication of the Protein Society · 2025Article
- Pentose phosphate pathway inhibition metabolically reprograms CD8+ T cells and disrupts CNS autoimmunity.JCI insight · 2025Article
- Pidotimod alleviated experimental autoimmune encephalomyelitis by regulating the balance of splenic lymphocytes.BMC immunology · 2025Article
- Diverse cell types establish a pathogenic immune environment in peripheral neuropathy.Journal of neuroinflammation · 2025Article
- Toward curing neurological autoimmune disorders: Biomarkers, immunological mechanisms, and therapeutic targets.Neuron · 2025Review
- Identification of the microglia-associated signature in experimental autoimmune encephalomyelitis.Frontiers in immunology · 2025Article
- The neuropathobiology of multiple sclerosis.Nature reviews. Neuroscience · 2024Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
CD8+ T cells outnumber CD4+ cells in multiple sclerosis (MS) lesions associated with disease progression, but the pathogenic role and antigenic targets of these clonally expanded effectors are unknown. Based on evidence that demyelination is necessary but not sufficient for disease progression in MS, we previously hypothesized that CNS-infiltrating CD8+ T cells specific for neuronal antigens directly drive the axonal and neuronal injury that leads to cumulative neurologic disability in patients with MS. We now show that demyelination induced expression of MHC class I on neurons and axons and resulted in presentation of a neuron-specific neoantigen (synapsin promoter-driven chicken ovalbumin) to antigen-specific CD8+ T cells (anti-ovalbumin OT-I TCR-transgenic T cells). These neuroantigen-specific effectors surveilled the CNS in the absence of demyelination but were not retained. However, upon induction of demyelination via cuprizone intoxication, neuroantigen-specific CD8+ T cells proliferated, accumulated in the CNS, and damaged neoantigen-expressing neurons and axons. We further report elevated neuronal expression of MHC class I and β2-microglobulin transcripts and protein in gray matter and white matter tracts in tissue from patients with MS. These findings support a pathogenic role for autoreactive anti-axonal and anti-neuronal CD8+ T cells in MS progression.
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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.