Humoral immune response to native eukaryotic prion protein correlates with anti-prion protection
AUTOR(ES)
Polymenidou, Magdalini
FONTE
National Academy of Sciences
RESUMO
Prion diseases are characterized by the deposition of an abnormal form (termed PrPSc) of the cellular prion protein (PrPC). Because antibodies to PrPC can antagonize deposition of PrPSc in cultured cells and mice, they may be useful for anti-prion therapy. However, induction of protective anti-prion immune responses in WT animals may be hindered by host tolerance. Here, we studied the cellular and molecular basis of tolerance to PrPC. Immunization of Prnpo/o mice with bacterially expressed PrP (PrPREC) resulted in vigorous humoral immune responses to PrPREC and native cell-surface PrPC. Instead, WT mice yielded antibodies that failed to recognize native PrPC despite immunoreactivity with PrPREC, even after immunization with PrP-PrP polyprotein and/or upon administration of anti-OX40 antibodies. Consequently, immunized WT mice experienced insignificantly delayed prion pathogenesis upon peripheral prion challenge. Anti-PrP immune responses in Prnpo/o mice were completely abrogated by transgenic expression of PrPC in B cells, T cells, neurons, or hepatocytes, but only moderately reduced by expression in myelinating cells, despite additional thymic Prnp transcription in each case. We conclude that tolerance to PrPC can coexist with immunoreactivity to PrPREC and does not depend on thymic PrPC expression. Its circumvention might represent an important step toward the development of effective anti-prion immunotherapy.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=521983Documentos Relacionados
- A Humoral Immune Response Confers Protection against Haemophilus ducreyi Infection
- Humoral immune response to plasmid protein pgp3 in patients with Chlamydia trachomatis infection.
- Humoral immune response to gonococcal infections.
- DNA Immunization with Trypanosoma cruzi HSP70 Fused to the KMP11 Protein Elicits a Cytotoxic and Humoral Immune Response against the Antigen and Leads to Protection
- Analysis of the Humoral Immune Response to Chlamydia Outer Membrane Protein 2