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Prepublished online as a Blood First Edition Paper on July 31, 2003; DOI 10.1182/blood-2003-05-1454.
Submitted May 13, 2003
Accepted July 22, 2003
CD4+CD25+ regulatory T cells inhibit immune mediated transgene rejection
David A Gross*, Marylene Leboeuf, Bernard Gjata, Olivier Danos, and Jean Davoust
Genethon, Evry, France
* Corresponding author; email: gross{at}genethon.fr.
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 TCR-transgenic animals, concomitant with gene transfer, down-regulates the anti-HA cytotoxic and B lymphocytes 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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