ArticleGlia2011
The majority of infiltrating CD8 T lymphocytes in multiple sclerosis lesions is insensitive to enhanced PD-L1 levels on CNS cells.
Article in Glia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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
29 citing papers in PubMed, 57 citations in OpenAlex.
- Natural Killer Cells Regulate Th17 Cells After Autologous Hematopoietic Stem Cell Transplantation for Relapsing Remitting Multiple Sclerosis.Frontiers in immunology · 2018Trial
- Regulatory T cells in stroke inflammation: Therapeutic perspectives.Neural regeneration research · 2026Article
- Nanomedicine targeting the PD-1/PD-L1 axis in autoimmune diseases: breaking conventional barriers to restore immune tolerance.Journal of nanobiotechnology · 2025Review
- Review
- Advances in immune checkpoint-based immunotherapies for multiple sclerosis: rationale and practice.Cell communication and signaling : CCS · 2023Review
- Astrocyte interferon-gamma signaling dampens inflammation during chronic central nervous system autoimmunity via PD-L1.Journal of neuroinflammation · 2023Article
- PD-L1 positive astrocytes attenuate inflammatory functions of PD-1 positive microglia in models of autoimmune neuroinflammation.Nature communications · 2023Article
- Women in the field of multiple sclerosis: How they contributed to paradigm shifts.Frontiers in molecular neuroscience · 2023Review
- IL-27 shapes the immune properties of human astrocytes and their impact on encountered human T lymphocytes.Journal of neuroinflammation · 2022Article
- Proteomic Alterations and Novel Markers of Neurotoxic Reactive Astrocytes in Human Induced Pluripotent Stem Cell Models.Frontiers in molecular neuroscience · 2022Article
- PD-1/PD-L Axis in Neuroinflammation: New Insights.Frontiers in neurology · 2022Review
- Not-so-opposite ends of the spectrum: CD8Nature immunology · 2021Review
- B cells in multiple sclerosis - from targeted depletion to immune reconstitution therapies.Nature reviews. Neurology · 2021Review
- Capturing T Lymphocytes' Dynamic Interactions With Human Neural Cells Using Time-Lapse Microscopy.Frontiers in immunology · 2021Article
- Renal cell carcinoma with central nervous system demyelination caused by nivolumab.IJU case reports · 2021Article
- Tumor-associated reactive astrocytes aid the evolution of immunosuppressive environment in glioblastoma.Nature communications · 2019Article
- Glial Cell Expression of PD-L1.International journal of molecular sciences · 2019Review
- Potential immunotherapy for Alzheimer disease and age-related dementia.Dialogues in clinical neuroscience · 2019Article
- NKG2D and Its Ligand MULT1 Contribute to Disease Progression in a Mouse Model of Multiple Sclerosis.Frontiers in immunology · 2019Article
- Tissue-resident memory T cells populate the human brain.Nature communications · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Central nervous system (CNS) cells locally modulate immune responses using numerous molecules that are not fully elucidated. Engagement of programmed death-1 (PD-1), expressed on activated T cells, by its ligands (PD-L1 or PD-L2) suppresses T-cell responses. Enhanced CNS PD-1 and PD-L1 expression has been documented in inflammatory murine models; however, human CNS data are still incomplete. We determined that human primary cultures of astrocytes, microglia, oligodendrocytes, or neurons expressed low or undetectable PD-L1 under basal conditions, but inflammatory cytokines significantly induced such expression, especially on astrocytes and microglia. Blocking PD-L1 expression in astrocytes using specific siRNA led to significantly increased CD8 T-cell responses (proliferation, cytokines, lytic enzyme). Thus, our results establish that inflamed human glial cells can express sufficient and functional PD-L1 to inhibit CD8 T cell responses. Extensive immunohistochemical analysis of postmortem brain tissues demonstrated a significantly greater PD-L1 expression in multiple sclerosis (MS) lesions compared with control tissues, which colocalized with astrocyte or microglia/macrophage cell markers. However, more than half of infiltrating CD8 T lymphocytes in MS lesions did not express PD-1, the cognate receptor. Thus, our results demonstrate that inflamed human CNS cells such as in MS lesions express significantly elevated PD-L1, providing a means to reduce CD8 T cell responses, but most of these infiltrating immune cells are devoid of PD-1 and thus insensitive to PD-L1/L2. Strategies aimed at inducing PD-1 on deleterious activated human CD8 T cells that are devoid of this receptor could provide therapeutic benefits since PD-L1 is already increased in the target organ.
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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.