CD4+CD25+ regulatory T cells inhibit immune-mediated transgene rejection.
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.
Gross
David-Alexandre
DA
Généthon/CNRS UMR 8115, 1bis, rue de l'Internationale, BP 60, 91002 Evry Cedex, France. gross@genethon.fr
Leboeuf
Marylene
M
Gjata
Bernard
B
Danos
Olivier
O
Davoust
Jean
J
D000818:Animals; D000910:Antibodies, Heterophile / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D000229:Dependovirus / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D007108:Immune Tolerance; D007114:Immunization; D007165:Immunosuppression Therapy / Q000379:methods*; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014161:Transduction, Genetic
D000910:Antibodies, Heterophile; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins