ArticleProceedings of the National Academy of Sciences of the United States of America2008
CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 277 papers, 1 of them a synthesis that pooled it.
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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
277 citing papers in PubMed, 1 synthesis or guideline pooled it, 460 citations in OpenAlex.
- Effects of diabetes mellitus on amyotrophic lateral sclerosis: a systematic review.BMC research notes · 2014Pooled it
- Safety and tolerability of tegoprubart in patients with amyotrophic lateral sclerosis: A Phase 2A clinical trial.PLoS medicine · 2024Trial
- Safety and efficacy of dimethyl fumarate in ALS: randomised controlled study.Annals of clinical and translational neurology · 2021Trial
- NP001 regulation of macrophage activation markers in ALS: a phase I clinical and biomarker study.Amyotrophic lateral sclerosis & frontotemporal degeneration · 2014Trial
- The thymus gland is a target and maintainer of amyotrophic lateral sclerosis pathophysiology.Brain, behavior, & immunity - health · 2026Article
- Cell-based immunotherapy for neurodegenerative disease: A promising avenue.Neural regeneration research · 2026Article
- TDP-43-immunity-microbiota axis in amyotrophic lateral sclerosis: A potential pathogenic mechanism.Neural regeneration research · 2026Article
- Fos regulates age-dependent neuroinflammation in a VAPP58S model of amyotrophic lateral sclerosis.Disease models & mechanisms · 2026Article
- Adaptive immunity in the pathogenesis of neurodegeneration.Nature immunology · 2026Review
- Immune signaling and function in neurodegeneration.The Journal of clinical investigation · 2026Review
- Renin-angiotensin system blockade attenuates brain mitochondrial dysfunction, oxidative stress, and neuroinflammation associated with hypertension, metabolic disorders, and aging.World journal of experimental medicine · 2026Review
- Immune imbalance between T helper 1, T helper 17 and regulatory T cells fuels amyotrophic lateral sclerosis pathogenesis: disease trajectory, diagnosis and therapeutic implications.Journal of neuroinflammation · 2026Review
- Natural Killer Cell Dysregulation During ALS Disease Progression: A Gene Expression Analysis.Neurology open access · 2026Article
- Engineering chimeric antigen receptor CD4 T cells for Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Comparative Analysis of T-Cell Signatures and Astroglial Reactivity in Parkinson's Pathology Across Animal Models with Distinct Regenerative Capacities.International journal of molecular sciences · 2026Article
- Neuroimmune phenotypes in brain aneurysms and neurodegenerative diseases.Frontiers in neuroscience · 2026Article
- Integrated multi-omics identification of m6A-SNP-related diagnostic biomarkers in amyotrophic lateral sclerosis.Frontiers in immunology · 2026Article
- Identification of Comprehensive Landscape of Peripheral Immunity and Chemokine-Related Genes in Amyotrophic Lateral Sclerosis.ImmunoTargets and therapy · 2026Article
- White Blood Cells in Neurodegenerative Diseases in the Context of Neuroinflammation.Molecular neurobiology · 2025Review
- Loss of C9orf72 impacts the peripheral neuromuscular system via immune dysregulation and accelerates the progression of amyotrophic lateral sclerosis in SOD-1 mutant mice.Journal of neuroinflammation · 2025Article
217 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Neuroinflammation, marked by gliosis and infiltrating T cells, is a prominent pathological feature in diverse models of dominantly inherited neurodegenerative diseases. Recent evidence derived from transgenic mice ubiquitously overexpressing mutant Cu(2+)/Zn(2+) superoxide dismutase (mSOD1), a chronic neurodegenerative model of inherited amyotrophic lateral sclerosis (ALS), indicates that glia with either a lack of or reduction in mSOD1 expression enhance motoneuron protection and slow disease progression. However, the contribution of T cells that are present at sites of motoneuron injury in mSOD1 transgenic mice is not known. Here we show that when mSOD1 mice were bred with mice lacking functional T cells or CD4+ T cells, motoneuron disease was accelerated, accompanied by unexpected attenuated morphological markers of gliosis, increased mRNA levels for proinflammatory cytokines and NOX2, and decreased levels of trophic factors and glial glutamate transporters. Bone marrow transplants reconstituted mice with T cells, prolonged survival, suppressed cytotoxicity, and restored glial activation. These results demonstrate for the first time in a model of chronic neurodegeneration that morphological activation of microglia and astroglia does not predict glial function, and that the presence of CD4+ T cells provides supportive neuroprotection by modulating the trophic/cytotoxic balance of glia. These glial/T-cell interactions establish a novel target for therapeutic intervention in ALS and possibly other neurodegenerative diseases.
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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.