NR AXVO
AU Sacquin,A.; Adam,M.; Crespeau,F.; Eloit,M.; Rosset,M.
TI Role of T CD8+ in the Control of Prion Diseases Assessed by Prnp-/- T CD8+ Transfer into C57Bl/6 Wild-type Mice
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.182
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Background: Cytotoxic T Lymphocytes (CTL) directed against PrP-derived peptides may possibly clear PrPsc accumulating cells and thus confer protection to scrapie infected mice. Up to now, few works have explored the CD8+ CTL repertoire specific for PrP in wild-type mice. Yet, as the PrP is a self-Ag, the major problem is the immune tolerance which must be bypassed at the risk of auto-immune manifestations. In a study presented in another poster, we demonstrated that injection of class I-restricted PrP peptides (227NP) to C57Bl/6 wild-type mice induced T cells to secrete IFNfx and to lyse peptide-pulsed RMAS cells in vitro and peptide-loaded splenocyte in vivo.
Aim(s)/Objective(s): We try to evaluate whether or not CTL against PrP could be an immune effector mechanism capable of controlling prion diseases.
Methods: To bypass natural tolerance, CTL against PrP were obtained by immunizing Prnp-/- Ly5.1 mice either with splenocytes from C57Bl/6 Ly5.1 wt mice or with the 227NP peptide in CpG/IFA. These cells were able to lyse PrP positive or peptidepulsed cells in vitro and in vivo. CD8+ T cells were purified and transferred in sublethally irradiated C57Bl/6 Ly5.2 wild-type mice. The capacity of anti-PrP CD8+ cells to protect against prion diseases will be evaluated after infection of these recipient mice with 139A murine scrapie.
Results: In both conditions of donor immunization, CD8+ Ly5.1 cells reconstituted irradiated recipients C57Bl/6 Ly5.2 and their level remained high during the asymptomatic period. No clinical signs of autoimmune reactions were observed and histopathological studies did not reveal significant cell infiltrations or destruction in secondary lymphoid organs and brain.We are currently monitoring in the blood the number and function of 227NP-specific CD8+ T cells by pentamer staining and IFN-specific secretion. Their potential efficiency in controlling the progression of scrapie will be checked on spleen PrPsc accumulation and survival of 139A-infected mice.
Conclusion: These experiments will analyse the role of PrP-specific CTL in the protection against prion diseases and might validate new immunological strategies.
AD A. Sacquin, M. Rosset, INSERM 712/Hopital St Antoine, France; M. Adam, M. Eloit, ENVA, UMR 1161, France; F. Crespeau, ENVA, UP d'Anatomie Pathologie, France
SP englisch
PO Schottland