th2-polarised prp-specific transgenic t-cells confer partial protection against murine scrapieth2-polarised prp-specific转基因t细胞提供部分保护小鼠痒病.pdfVIP

Th2-polarised PrP-specific Transgenic T-cells Confer Partial Protection against Murine Scrapie 1,2 ´ 1,2 1,2¤a 3 ´ 1,2¤b Saci Iken , Veronique Bachy , Pauline Gourdain , Annick Lim , Sylvie Gregoire , Thomas Chaigneau1,2, Pierre Aucouturier1,2, Claude Carnaud1,2* ˆ ˆ 1 UPMC Univ Paris 6, UMR_S 938, Centre de Recherche Hopital Saint-Antoine, Paris, France, 2 INSERM, UMR_S 938, Centre de Recherche Hopital Saint-Antoine, Paris, ´ ´ France, 3 Unite du Developpement des Lymphocytes, Institut Pasteur, Paris and INSERM U668, Paris, France Abstract Several hurdles must be overcome in order to achieve efficient and safe immunotherapy against conformational neurodegenerative diseases. In prion diseases, the main difficulty is that the prion protein is tolerated as a self protein, which prevents powerful immune responses. Passive antibody therapy is effective only during early, asymptomatic disease, well before diagnosis is made. If efficient immunotherapy of prion diseases is to be achieved, it is crucial to understand precisely how immune tolerance against the prion protein can be overcome and which effector pathways may delay disease progression. To this end, we generated a transgenic mouse that expresses the ß-chain of a T cell receptor recognizing a PrP epitope presented by the class II major histocompatibility complex. The fact that the constraint is applied to only one TCR chain allows adaptation of the other chain according to the presence or absence of