dendritic cell-mediated-immunization with xenogenic prp and adenoviral vectors breaks tolerance and prolongs mice survival against experimental scrapie树突cell-mediated-immunization与异种的prp和运载体减免宽容和延长小鼠生存实验痒病.pdfVIP

Dendritic Cell-Mediated-Immunization with Xenogenic PrP and Adenoviral Vectors Breaks Tolerance and Prolongs Mice Survival against Experimental Scrapie 1,2 1,2 3 1,2 Martine Bruley Rosset *, Antoine Sacquin , Sylvie Lecollinet , Thomas Chaigneau , Micheline 3 4 3 Adam , Franc¸ois Crespeau , Marc Eloit ˆ 1 INSERM UMR 938, Paris, France, 2 UPMC Univ Paris 06, Hopital Saint-Antoine, Saint-Antoine, Paris, France, 3 UMR1161 Virologie, INRA, AFSSA, ENVA, Ecole Nationale ´ ´ ´ ´ Veterinaire d’Alfort, Maisons Alfort, France, 4 Laboratoire d’anatomopathologie, Ecole Nationale Veterinaire d’Alfort, Maisons Alfort, France Abstract c Sc In prion diseases, PrP , a widely expressed protein, is transformed into a pathogenic form called PrP , which is in itself infectious. Antibodies directed against PrPc have been shown to inhibit PrPc to PrPSc conversion in vitro and protect in vivo from disease. Other effectors with potential to eliminate PrPSc-producing cells are cytotoxic T cells directed against PrP- derived peptides but their ability to protect or to induce deleterious autoimmune reactions is not known. The natural tolerance to PrPc makes difficult to raise efficient adaptive responses. To break tolerance, adenovirus (Ad) encoding human PrP (hPrP) or control Ad were administered to wild-type mice by direct injection or by transfer of Ad-t