NR AWBH
AU Bachy,V.; Gourdain,P.; Gregoire,S.; Bruley Rosset,M.; Aucouturier,P.; Carnaud,C.
TI Adoptive immuno-cell therapy in prion diseases: a study of some prerequisites
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions THE-02
PT Konferenz-Poster
AB Adoptive immuno-cell therapy could circumvent some of the limitations reported with active vaccination or passive antibody transfer against mouse scrapie. These difficulties mainly stem from the strong tolerogenicity of PrP and from the relative inaccessibility of the brain to antibodies. We have presently explored two alternative strategies of adoptive cell therapy. A first one consists in adoptively infusing into wild-type mice, T cells from Prnp-/- donors which were immunized against major mouse PrP epitopes. Another one relies on the administration into wild-type recipients, of live activated bone marrow-derived dendritic cells (DCs) loaded with MHC class II-restricted immunogenic peptides of mouse PrP. Regarding the first strategy, we have asked whether adoptively transferred T cells would survive to the various forms of peripheral tolerance, retain their immune reactivity, cooperate with host B cells, and eventually retard scrapie progression without causing adverse autoimmune manifestations. Our results do clearly demonstrate a persistence of the adopted T cells in the wild-type hosts up to 3 months after transfer, with an intact capacity to respond to PrP epitopes and to cooperate with B cells for antibody production. Furthermore, such T cells retard scrapie lymphoinvasion with no apparent clinical or histological signs of autoimmunity. With respect to the loaded-DC strategy, we have looked at the capacity of such cells to activate a helper T and B lymphocyte repertoire specific of PrP. Loaded DCs elicit a reproducible antibody response to native, membrane-bound PrP, even in wild-type mice, presumably harbouring a strongly repressed B cell repertoire. These results provide encouraging answers to some major prerequisites for adoptive cell therapy: 1) infused anti-PrP T cells are not ineluctably tolerized in a PrP-positive environment, 2) a persisting B cell repertoire to native PrP can be activated, notably by peptide-loaded DCs in wild-type recipients and 3) adoptive cell therapy appears to be active against prion propagation in scrapieinfected mice.
AD INSERM U-712, Hôpital Saint-Antoine, Paris, France. E-mail: carnaud@st-antoine.inserm.fr
SP englisch
PO Italien