ArticleBlood2009
Silencing of T lymphocytes by antigen-driven programmed death in recombinant adeno-associated virus vector-mediated gene therapy.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
38 citing papers in PubMed, 44 citations in OpenAlex.
- Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Trial
- Trial
- Limb-girdle muscular dystrophy type 2D gene therapy restores alpha-sarcoglycan and associated proteins.Annals of neurology · 2009Trial
- Immune-driven gene expression loss following intramuscular AAV delivery to non-human primates is only transient.Molecular therapy. Methods & clinical development · 2025Article
- Dual FKRP/FST gene therapy normalizes ambulation, increases strength, decreases pathology, and amplifies gene expression in LGMDR9 mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Tumor antigen-loaded AAV vaccine drives protective immunity in a melanoma animal model.Molecular therapy. Methods & clinical development · 2023Article
- Therapeutic efficacy of rscAAVrh74.miniCMV.Molecular therapy. Methods & clinical development · 2022Article
- Effect of CpG Depletion of Vector Genome on CD8Frontiers in immunology · 2021Article
- Immune Response Mechanisms against AAV Vectors in Animal Models.Molecular therapy. Methods & clinical development · 2020Review
- rAAVrh74.MCK.Molecular therapy. Methods & clinical development · 2019Article
- Complexity of immune responses to AAV transgene products - Example of factor IX.Cellular immunology · 2019Review
- Five Years of Successful Inducible Transgene Expression Following Locoregional Adeno-Associated Virus Delivery in Nonhuman Primates with No Detectable Immunity.Human gene therapy · 2019Article
- Cas9 immunity creates challenges for CRISPR gene editing therapies.Nature communications · 2018Article
- Induction of T-Cell Infiltration and Programmed Death Ligand 2 Expression by Adeno-Associated Virus in Rhesus Macaque Skeletal Muscle and Modulation by Prednisone.Human gene therapy · 2017Article
- Regulatory and Exhausted T Cell Responses to AAV Capsid.Human gene therapy · 2017Article
- A multifunctional AAV-CRISPR-Cas9 and its host response.Nature methods · 2016Article
- Progress and prospects of gene therapy clinical trials for the muscular dystrophies.Human molecular genetics · 2016Review
- Efficient and Targeted Transduction of Nonhuman Primate Liver With Systemically Delivered Optimized AAV3B Vectors.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- The Skeletal Muscle Environment and Its Role in Immunity and Tolerance to AAV Vector-Mediated Gene Transfer.Current gene therapy · 2015Review
- A dystrophic muscle broadens the contribution and activation of immune cells reacting to rAAV gene transfer.Gene therapy · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Recombinant adeno-associated virus (rAAV) vectors are considered promising for human gene replacement because they facilitate stable expression of therapeutic proteins in transduced tissues. Whether the success of gene therapy will be influenced by cellular immune responses targeting transgene-encoded proteins that are potentially immunogenic is unknown. Here we characterized CD8(+) T-cell activity against beta-galactosidase and enhanced green fluorescent protein, model antigens containing major histocompatibility complex (MHC) class I epitopes that are constitutively produced in murine skeletal muscle after rAAV vector transduction. Antigen-specific CD8(+) T cells were detected in the spleen and liver of mice within 7 days of muscle transduction. CD8(+) T-cell frequencies in these organs were stable, and effector functions were intact for months despite ongoing antigen production in muscle. CD8(+) T cells also infiltrated transduced muscle, where frequencies were at least 5-fold higher than in untransduced spleen and liver. Significantly, the majority of antigen-specific CD8(+) T cells in vector-transduced muscle were not functional. Loss of function in the muscle was associated with programmed death of the effector cells. Stable gene expression therefore depended on selective death of CD8(+) T cells at the site of antigen production, an effective mechanism for subverting immunity that is also potentially reversible.
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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.