ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
Immune-mediated loss of transgene expression from virally transduced brain cells is irreversible, mediated by IFNγ, perforin, and TNFα, and due to the elimination of transduced cells.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- A Confocal Microscopic Study of Gene Transfer into the Mesencephalic Tegmentum of Juvenile Chum Salmon,International journal of molecular sciences · 2021Article
- A novel miR1983-TLR7-IFNβ circuit licenses NK cells to kill glioma cells, and is under the control of galectin-1.Oncoimmunology · 2021Article
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- Evolutionary basis of a new gene- and immune-therapeutic approach for the treatment of malignant brain tumors: from mice to clinical trials for glioma patients.Clinical immunology (Orlando, Fla.) · 2018Review
- Viral vectors for therapy of neurologic diseases.Neuropharmacology · 2017Review
- Article
- Targeting Motor End Plates for Delivery of Adenoviruses: An Approach to Maximize Uptake and Transduction of Spinal Cord Motor Neurons.Scientific reports · 2016Article
- Slow AAV2 clearance from the brain of nonhuman primates and anti-capsid immune response.Gene therapy · 2016Article
- The Long and Winding Road: From the High-Affinity Choline Uptake Site to Clinical Trials for Malignant Brain Tumors.Advances in pharmacology (San Diego, Calif.) · 2016Review
- Kupfer-type immunological synapses in vivo: Raison D'être of SMAC.Immunology and cell biology · 2015Review
- Consensus guidelines for the detection of immunogenic cell death.Oncoimmunology · 2014Review
- Natural killer cells eradicate galectin-1-deficient glioma in the absence of adaptive immunity.Cancer research · 2014Article
- Adenoviral vector-mediated gene therapy for gliomas: coming of age.Expert opinion on biological therapy · 2014Review
- Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
The adaptive immune response to viral vectors reduces vector-mediated transgene expression from the brain. It is unknown, however, whether this loss is caused by functional downregulation of transgene expression or death of transduced cells. Herein, we demonstrate that during the elimination of transgene expression, the brain becomes infiltrated with CD4(+) and CD8(+) T cells and that these T cells are necessary for transgene elimination. Further, the loss of transgene-expressing brain cells fails to occur in the absence of IFNγ, perforin, and TNFα receptor. Two methods to induce severe immune suppression in immunized animals also fail to restitute transgene expression, demonstrating the irreversibility of this process. The need for cytotoxic molecules and the irreversibility of the reduction in transgene expression suggested to us that elimination of transduced cells is responsible for the loss of transgene expression. A new experimental paradigm that discriminates between downregulation of transgene expression and the elimination of transduced cells demonstrates that transduced cells are lost from the brain upon the induction of a specific antiviral immune response. We conclude that the anti-adenoviral immune response reduces transgene expression in the brain through loss of transduced cells.
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