NR AXNI
AU Gourdain,P.; Gregoire,S.; Bachy,V.; Chaigneau,T.; Renault,I.; Dorban,G.; Rosset,M.B.; Aucouturier,P.; Carnaud,C.
TI Resistance Against Mouse Scrapie can be Conferred by Lymphocytes Primed Against the Prion Protein
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.63
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB Recent literature suggests that neurodegenerative conditions such as Alzheimer or prion diseases are tractable by immunopreventive or immunotherapeutical approaches. With respect to prion diseases, passive transfer of Ab directed at PrP or active immunisation have been tested with promising, but still limited results. There are many reasons to the encountered difficulties: the long and silent incubation period, the rapid neurological degradation once disease is declared, the poor accessibility of the brain to immunological agents, notably Ab, the lack of clear knowledge of the protective mechanisms that ought to be favoured and the strong unresponsiveness of the immune system to self PrP. Adoptive cell transfer could overcome some of those difficulties, by supplying the declared or the suspected patient with long-lived immune effector cells, selected and profiled for optimal migration to the sites of prion expansion and for most effective protection. In order to put these ideas to test, we have conceived a mouse model of transfer in which lymphocytes are primed in a PrPdeficient animal, which is thus fully reactive to PrP and are subsequently injected into a recipient which is histocompatible with the donor, totally or partially lymphopenic for insuring a good expansion of the transferred cells and PrP-sufficient for permissiveness to scrapie infection. Using this model, we presently report evidence that PrP-primed spleen cells although not inducing definitive remissions, can nevertheless significantly delay the onset of mouse scrapie and its neurological evolution, provided the effector cells are periodically re-boosted in the host with a strong antigenic peptide of PrP. T cells transferred alone can under similar conditions of periodic recall, limit PrPsc extension in secondary lymphoid organs. The model provides further indications regarding peripheral manifestations of tolerance exerted against the transferred lymphocytes and how they can be overcome. It also shows that, although none of the recipients develop clinical signs of neurological autoimmunity, abnormally elevated numbers of donor T cells can be identified in the different sectors of the host brain.
AD P. Gourdain, V. Bachy, T. Chaigneau, M. Rosset, P. Aucouturier, C. Carnaud, Hospital Saint-Antoine, France; S. Gregoire, Hospital Pitie-Salpetriere, France; I. Renault, Hospital St-Antoine, France; G. Dorban, University of Liege, Belgium
SP englisch
PO Schottland
EA pdf-Datei und Poster (Posterautoren reduziert um V. Bachy)