Gross David-Alexandre, Leboeuf Marylene, Gjata Bernard, Danos Olivier, Davoust Jean
Généthon/CNRS UMR 8115, 1bis, rue de l'Internationale, BP 60, 91002 Evry Cedex, France.
Blood. 2003 Dec 15;102(13):4326-8. doi: 10.1182/blood-2003-05-1454. Epub 2003 Jul 31.
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.
与细胞移植一样，基因治疗常常受到新表达抗原免疫排斥的限制。在肌肉基因转移模型中，腺相关病毒（AAV）介导的流感血凝素（HA）膜蛋白传递因强烈的免疫反应而受损，这种免疫反应导致转导纤维迅速被排斥。我们在此表明，从T细胞受体（TCR）转基因动物中注射HA特异性CD4+CD25+ T细胞，并与基因转移同时进行，可下调抗HA细胞毒性和B淋巴细胞反应，并使HA在肌肉中持续表达。这首次证明，抗原特异性CD4+CD25+调节性T细胞的过继转移可用于诱导实体组织中持续的转基因植入。
