Contribution of antibody and T cell-specific responses to the progression of 139A-scrapie in C57BL/6 mice immunized with prion protein peptides

Sacquin, Antoine, Bergot, Anne Sophie, Aucouturier, Pierre and Bruley-Rosset, Martine (2008) Contribution of antibody and T cell-specific responses to the progression of 139A-scrapie in C57BL/6 mice immunized with prion protein peptides. Journal of Immunology, 181 1: 768-775.

Author Sacquin, Antoine
Bergot, Anne Sophie
Aucouturier, Pierre
Bruley-Rosset, Martine
Title Contribution of antibody and T cell-specific responses to the progression of 139A-scrapie in C57BL/6 mice immunized with prion protein peptides
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
1550-6606
Publication date 2008-07
Sub-type Article (original research)
Volume 181
Issue 1
Start page 768
End page 775
Total pages 8
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Language eng
Formatted abstract
Prion diseases are associated with the conversion of the normal host cellular prion protein to an abnormal protease-resistant (PrPres) associated with infectivity. No specific immune response against prions develops during infection due to the strong tolerance to cellular prion protein. We examined the protective potential on prion diseases of immune responses elicited in C57BL/6 mice with PrP peptides 98-127 (P5) or 158-187 (P9) with CpG. After immunization, P5-treated mice developed high titer and long-lasting Abs, and P9-treated mice developed transient IFN-γ secreting T cells and poor and variable Ab responses. Both treatments impaired early accumulation of PrPres in the spleen and prolonged survival of mice infected with 139A scrapie. Additional P9 boosts after 139A infection sustained the T cell response and partially inhibited PrPres early accumulation but did not improve the survival. Surprisingly, when P9 injections were started 1 mo after infection and repeated subsequently, specific T cell and Ab responses were impaired and no beneficial effect on prion disease was observed. After a single injection of P9, the number of IFN-γ secreting CD4+ T cells was also reduced in mice 8- to 10-wk postinfection compared with healthy mice. In vivo and in vitro removal of CD4+CD25+ T cells restored the T cell response to P9 in infected mice. In conclusion, CD4+ T cells as well as Abs might participate to the protection against scrapie. Of importance, the peripheral accumulation of PrPres during infection negatively interferes with the development of T and B cell responses to PrP and regulatory T cells might contribute to this phenomenon. Copyright © 2008 by The American Association of Immunologists, Inc.
Keyword Wild-Type Mice
Self-Tolerance
Infected-Cells
Monoclonal-Antibodies
Scrapie Agent
Disease
Prp
Cpg
Vaccination
Replication
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
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