CD4+CD25+ regulatory T cells inhibit immune-mediated transgene rejection |
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Authors: | Gross David-Alexandre Leboeuf Marylene Gjata Bernard Danos Olivier Davoust Jean |
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Institution: | Généthon/CNRS UMR 8115, 1bis, rue de l'Internationale, BP 60, 91002 Evry Cedex, France. gross@genethon.fr |
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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. |
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