Abstract
Like cellular transplantation, gene therapy is often limited by immune rejection of the newly expressed antigen. In a model of gene transfer in muscle, delivery of the influenza hemagglutinin (HA) membrane protein by adeno-associated virus (AAV) is impaired by a strong immune response that leads to a rapid rejection of the transduced fibers. We show here that injection of HA-specific CD4+CD25+ T cells from T-cell receptor (TCR)-transgenic animals, concomitant with gene transfer, down-regulates the anti-HA cytotoxic and B-lymphocyte responses and enables persistent HA expression in muscle. This demonstrates for the first time that adoptive transfer of antigen-specific CD4+CD25+ regulatory T cells can be used to induce sustained transgene engraftment in solid tissues.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Heterophile / biosynthesis
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / transplantation
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Dependovirus / genetics
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Genetic Vectors / genetics
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Hemagglutinin Glycoproteins, Influenza Virus / biosynthesis
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Hemagglutinin Glycoproteins, Influenza Virus / genetics
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Hemagglutinin Glycoproteins, Influenza Virus / immunology*
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Immune Tolerance
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Immunization
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Immunosuppression Therapy / methods*
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Lymphocyte Subsets / immunology*
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Lymphocyte Subsets / transplantation
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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Muscle, Skeletal / metabolism
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Receptors, Antigen, T-Cell / immunology*
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Receptors, Interleukin-2 / analysis
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Recombinant Fusion Proteins / immunology
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Transduction, Genetic*
Substances
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Antibodies, Heterophile
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Hemagglutinin Glycoproteins, Influenza Virus
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Receptors, Antigen, T-Cell
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Receptors, Interleukin-2
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Recombinant Fusion Proteins