Document Detail

Th2-polarised PrP-specific transgenic T-cells confer partial protection against murine scrapie.
MedLine Citation:
PMID:  21909267     Owner:  NLM     Status:  MEDLINE    
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 tolerogenic PrP. We first show that transgene-bearing T cells, pairing with rearranged α-chains conferring anti-PrP specificity, are systematically eliminated during ontogeny in PrP+ mice, suggesting that precursors with good functional avidity are rare in a normal individual. Second, we show that transgene-bearing T cells with anti-PrP specificity are not suppressed when transferred into PrP+ recipients and proliferate more extensively in a prion-infected host. Finally, such T cells provide protection through a cell-mediated pathway involving IL-4 production. These findings support the idea that cell-mediated immunity in neurodegenerative conditions may not be necessarily detrimental and may even contribute, when properly controlled, to the resolution of pathological processes.
Saci Iken; Véronique Bachy; Pauline Gourdain; Annick Lim; Sylvie Grégoire; Thomas Chaigneau; Pierre Aucouturier; Claude Carnaud
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-09-01
Journal Detail:
Title:  PLoS pathogens     Volume:  7     ISSN:  1553-7374     ISO Abbreviation:  PLoS Pathog.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-12     Completed Date:  2012-01-05     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  101238921     Medline TA:  PLoS Pathog     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e1002216     Citation Subset:  IM    
UPMC Univ Paris 6, UMR_S 938, Centre de Recherche Hôpital Saint-Antoine, Paris, France.
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MeSH Terms
Adoptive Transfer
CD4-Positive T-Lymphocytes / transplantation
Complementarity Determining Regions
Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
Mice, Transgenic
PrPSc Proteins / immunology
Prions / immunology*
Receptors, Antigen, T-Cell, alpha-beta / immunology
Scrapie / prevention & control*
Th2 Cells / immunology*
Reg. No./Substance:
0/Complementarity Determining Regions; 0/PrPSc Proteins; 0/Prions; 0/Receptors, Antigen, T-Cell, alpha-beta; 207137-56-2/Interleukin-4

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