ArticleBMC immunology2004
In situ transduction of stromal cells and thymocytes upon intrathymic injection of lentiviral vectors.
Article in BMC immunology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Editing T cell repertoire by thymic epithelial cell-directed gene transfer abrogates risk of type 1 diabetes development.Molecular therapy. Methods & clinical development · 2022Article
- In Vivo Lentiviral Gene Delivery of HLA-DR and Vaccination of Humanized Mice for Improving the Human T and B Cell Immune Reconstitution.Biomedicines · 2021Article
- Thymic rejuvenation and aging.Current opinion in immunology · 2013Review
- Immunomodulatory strategies prevent the development of autoimmune emphysema.Respiratory research · 2010Article
- Induction of immune tolerance to a therapeutic protein by intrathymic gene delivery.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Article
- Efficient intrathymic gene transfer following in situ administration of a rAAV serotype 8 vector in mice and nonhuman primates.Molecular therapy : the journal of the American Society of Gene Therapy · 2009Article
- Immunopathogenesis of feline immunodeficiency virus infection in the fetal and neonatal cat.Frontiers in bioscience : a journal and virtual library · 2007Review
- Human gene therapy and imaging in neurological diseases.European journal of nuclear medicine and molecular imaging · 2005Review
- A new direction for gene therapy: intrathymic T cell-specific lentiviral gene transfer.The Journal of clinical investigation · 2005Article
- In vivo correction of ZAP-70 immunodeficiency by intrathymic gene transfer.The Journal of clinical investigation · 2005Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe thymus is the primary site for T-cell development and induction of self-tolerance. Previous approaches towards manipulation of T-cell differentiation have used intrathymic injection of antigens, as proteins, cells or adenoviruses, leading to transient expression of the foreign protein. Lentiviral vectors, due to their unique ability to integrate into the genome of quiescent cells, may be best suited for long-term expression of a transgene in the thymus.
resultsYoung adult mice were injected in the thymus with lentiviral vectors expressing eGFP or the hemaglutinin of the Influenza virus under the control of the ubiquitous phospho glycerate kinase promoter. Thymi were examined 5 to 90 days thereafter directly under a UV-light microscope and by flow cytometry. Intrathymic injection of lentiviral vectors predominantly results in infection of stromal cells that could be detected for at least 3 months. Importantly, hemaglutinin expression by thymic stromal cells mediated negative selection of thymocytes expressing the cognate T-cell receptor. In addition and despite the low multiplicity of infection, transduced thymocytes were also detected, even 30 days after injection.
conclusionsOur results demonstrate that intrathymic delivery of a lentiviral vector is an efficient means for stable expression of a foreign gene in the thymus. This new method of gene delivery may prove useful for induction of tolerance to a specific antigen and for gene therapy of severe combined immunodeficiencies.
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