{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:16:37Z","timestamp":1790392597812,"version":"4.1.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2008,7,1]],"date-time":"2008-07-01T00:00:00Z","timestamp":1214870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u2013127 (P5) or 158\u2013187 (P9) with CpG. After immunization, P5-treated mice developed high titer and long-lasting Abs, and P9-treated mice developed transient IFN-\u03b3 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-\u03b3 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.<\/jats:p>","DOI":"10.4049\/jimmunol.181.1.768","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:04:22Z","timestamp":1397847862000},"page":"768-775","source":"Crossref","is-referenced-by-count":12,"title":["Contribution of Antibody and T Cell-Specific Responses to the Progression of 139A-Scrapie in C57BL\/6 Mice Immunized with Prion Protein Peptides"],"prefix":"10.1093","volume":"181","author":[{"given":"Antoine","family":"Sacquin","sequence":"first","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale UMRS 893, Paris; Universit\u00e9 Pierre et Marie Curie Univ Paris 06, H\u00f4pital Saint-Antoine , Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Sophie","family":"Bergot","sequence":"additional","affiliation":[{"name":"Centre National de la Recherche Scientifique\/Unit\u00e9 Mixte de Recherche; Universit\u00e9 Pierre et Marie Curie Univ Paris 06, H\u00f4pital La Piti\u00e9 Salpetri\u00e8re , Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Aucouturier","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale UMRS 893, Paris; Universit\u00e9 Pierre et Marie Curie Univ Paris 06, H\u00f4pital Saint-Antoine , Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Bruley-Rosset","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale UMRS 893, Paris; Universit\u00e9 Pierre et Marie Curie Univ Paris 06, H\u00f4pital Saint-Antoine , Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,7,1]]},"reference":[{"key":"2026012807123408000_R1","first-page":"13363","article-title":"Prions.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1998"},{"key":"2026012807123408000_R2","first-page":"337","article-title":"Prion protein biology.","volume-title":"Cell","year":"1998"},{"key":"2026012807123408000_R3","first-page":"107","article-title":"The immune system and prion diseases: a relationship of complicity and blindness.","volume-title":"J. Leukocyte Biol.","year":"2002"},{"key":"2026012807123408000_R4","first-page":"1407","article-title":"Failure to demonstrate a humoral immune response to scrapie infection in mice.","volume-title":"J. Immunol.","year":"1973"},{"key":"2026012807123408000_R5","first-page":"149","article-title":"Nearly ubiquitous tissue distribution of the scrapie agent precursor protein.","volume-title":"Neurology","year":"1992"},{"key":"2026012807123408000_R6","first-page":"916","article-title":"Peripherally administered antibodies against amyloid \u03b2-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease.","volume-title":"Nat. Med.","year":"2000"},{"key":"2026012807123408000_R7","first-page":"979","article-title":"A\u03b2 peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer\u2019s disease.","volume-title":"Nature","year":"2000"},{"key":"2026012807123408000_R8","first-page":"9295","article-title":"Scrapie prion protein accumulation by scrapie-infected neuroblastoma cells abrogated by exposure to a prion protein antibody.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2001"},{"key":"2026012807123408000_R9","first-page":"739","article-title":"Antibodies inhibit prion propagation and clear cell cultures of prion infectivity.","volume-title":"Nature","year":"2001"},{"key":"2026012807123408000_R10","first-page":"39671","article-title":"PrPSc binding antibodies are potent inhibitors of prion replication in cell lines.","volume-title":"J. Biol. Chem.","year":"2004"},{"key":"2026012807123408000_R11","first-page":"18524","article-title":"Polyclonal anti-PrP auto-antibodies induced with dimeric PrP interfere efficiently with PrPSc propagation in prion-infected cells.","volume-title":"J. Biol. Chem.","year":"2003"},{"key":"2026012807123408000_R12","first-page":"2635","article-title":"Clearance and prevention of prion infection in cell culture by anti-PrP antibodies.","volume-title":"Eur. J. Neurosci.","year":"2006"},{"key":"2026012807123408000_R13","first-page":"80","article-title":"Monoclonal antibodies inhibit prion replication and delay the development of prion disease.","volume-title":"Nature","year":"2003"},{"key":"2026012807123408000_R14","first-page":"178","article-title":"Prevention of scrapie pathogenesis by transgenic expression of anti-prion protein antibodies.","volume-title":"Science","year":"2001"},{"key":"2026012807123408000_R15","first-page":"187","article-title":"Immunization with a synthetic prion protein-derived peptide prolongs survival times of mice orally exposed to the scrapie agent.","volume-title":"Neurosci. Lett.","year":"2003"},{"key":"2026012807123408000_R16","first-page":"2862","article-title":"Decrease in pathology and progression of scrapie after immunization with synthetic prion protein peptides in hamsters.","volume-title":"Vaccine","year":"2005"},{"key":"2026012807123408000_R17","first-page":"985","article-title":"Immunization with recombinant bovine but not mouse protein delays the onset of disease in mice inoculated with a mouse-adapted prion.","volume-title":"Vaccine","year":"2007"},{"key":"2026012807123408000_R18","first-page":"4033","article-title":"Circumventing tolerance to the prion protein (PrP): vaccination with PrPdisplaying retrovirus particles induces humoral immune responses against the native form of cellular PrP.","volume-title":"J. Virol.","year":"2005"},{"key":"2026012807123408000_R19","first-page":"1747","article-title":"Vaccination with prion peptide-dispaying papillomavirus-like particles induces autoantibodies to normal prion protein that interfere with pathologic prion protein production in infected cells.","volume-title":"FEBS J.","year":"2007"},{"key":"2026012807123408000_R20","first-page":"2815","article-title":"Enhanced mucosal immunogenicity of prion protein following fusion with B subunit of Escherichia coli heat-labile enterotoxin.","volume-title":"Vaccine","year":"2006"},{"key":"2026012807123408000_R21","first-page":"242","article-title":"Intranasal immunization of Balb\/c mice against prion protein attenuates orally acquired transmissible spongiform encephalopathy.","volume-title":"Vaccine","year":"2006"},{"key":"2026012807123408000_R22","first-page":"413","article-title":"Mucosal vaccination delays or prevents prion infection via an oral route.","volume-title":"Neuroscience","year":"2005"},{"key":"2026012807123408000_R23","first-page":"6443","article-title":"The murine B-cell repertoire is severely selected against endogenous cellular prion protein.","volume-title":"J. Immunol.","year":"2005"},{"key":"2026012807123408000_R24","first-page":"1059","article-title":"The human prion protein residue 129 polymorphism lies within a cluster of epitopes for T cell recognition.","volume-title":"J. Neuropathol. Exp. Neurol.","year":"2006"},{"key":"2026012807123408000_R25","first-page":"3256","article-title":"Protein conformation significantly influences immune responses to prion protein.","volume-title":"J. Immunol.","year":"2005"},{"key":"2026012807123408000_R26","first-page":"2338","article-title":"Modulation of proteinase-K resistant prion protein by prion peptide immunization.","volume-title":"Eur. J. Immunol.","year":"2001"},{"key":"2026012807123408000_R27","first-page":"3799","article-title":"T cells infiltrate the brain in murine and human transmissible spongiform encephalopathies.","volume-title":"J. Virol.","year":"2003"},{"key":"2026012807123408000_R28","first-page":"629","article-title":"CD4+ T cell-mediated immunity against prion proteins.","volume-title":"Cell Mol. Life Sci.","year":"2003"},{"key":"2026012807123408000_R29","first-page":"125","article-title":"Identification of two immunogenic domains of the prion protein-PrP-which activate class-I restricted T cells and elicit antibody responses against the native molecule.","volume-title":"J. Leukocyte Biol.","year":"2004"},{"key":"2026012807123408000_R30","first-page":"5168","article-title":"Breaking immune tolerance to the prion protein (PrP) with PrP peptides plus oligo-CpG in mice.","volume-title":"J. Immunol.","year":"2004"},{"key":"2026012807123408000_R31","first-page":"2353","article-title":"Experimental scrapie in \u201cplt\u201d mice: an assessement of the role of dendritic-cell migration in the pathogenesis of prion diseases.","volume-title":"J. Gen. Virol.","year":"2007"},{"key":"2026012807123408000_R32","first-page":"703","article-title":"Infected splenic dendritic cells are sufficient for prion transmission to the CNS in mouse scrapie.","volume-title":"J. Clin. Invest.","year":"2001"},{"key":"2026012807123408000_R33","first-page":"14670","article-title":"Humoral immune response to native eukariotic prion protein correlates with anti-prion protection.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2004"},{"key":"2026012807123408000_R34","first-page":"11247","article-title":"Screening of 145 anti-PrP monoclonal antibodies for their capacity to inhibit PrPSc replication in infected cells.","volume-title":"J. Biol. Chem.","year":"2005"},{"key":"2026012807123408000_R35","first-page":"9970","article-title":"DNA vaccination can break immunological tolerance to PrP in wild-type mice and attenuates prion disease after intracerebral challenge.","volume-title":"J. Virol.","year":"2006"},{"key":"2026012807123408000_R36","first-page":"2797","article-title":"Polylactide-coglycolide microspheres co-encapsulating recombinant tandem prion protein with CpG-oligonucleotide break self-tolerance to prion protein in wild-type mice and induce CD4 and CD8 T cell responses.","volume-title":"J. Immunol.","year":"2007"},{"key":"2026012807123408000_R37","first-page":"1176","article-title":"Evidence for normal cell-mediated immunity in scrapie-infected mice.","volume-title":"Infect. Immun.","year":"1981"},{"key":"2026012807123408000_R38","first-page":"233","article-title":"Immunological responsivness of scrapie infected mice.","volume-title":"J. Comp. Pathol.","year":"1969"},{"key":"2026012807123408000_R39","first-page":"1986","article-title":"Suppression of polyclonal B cell activation in scrapie-infected C3H\/HeJ mice.","volume-title":"J. Immunol.","year":"1978"},{"key":"2026012807123408000_R40","first-page":"682","article-title":"Restoring function in exhausted CD8 T cells during chronic viral infection.","volume-title":"Nature","year":"2006"},{"key":"2026012807123408000_R41","first-page":"531","article-title":"Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses.","volume-title":"Annu. Rev. Immunol.","year":"2004"},{"key":"2026012807123408000_R42","first-page":"353","article-title":"Natural regulatory T cells in infectious disease.","volume-title":"Nat. Immunol.","year":"2005"},{"key":"2026012807123408000_R43","first-page":"3982","article-title":"Persistence of physiological self antigen is required foe the regulation of self tolerance.","volume-title":"J. Immunol.","year":"2000"},{"key":"2026012807123408000_R44","first-page":"709","article-title":"CpG motifs in bacterial DNA and their immune effects.","volume-title":"Annu. Rev. Immunol.","year":"2002"},{"key":"2026012807123408000_R45","first-page":"5834","article-title":"CpG and LPS can interfere negatively with prion clearance in macrophage and microglial cells.","volume-title":"FEBS J.","year":"2007"},{"key":"2026012807123408000_R46","first-page":"229","article-title":"Postexposure prophylaxis against prion disease with a stimulator of innate immunity.","volume-title":"Lancet","year":"2002"},{"key":"2026012807123408000_R47","first-page":"187","article-title":"Lymphoid folicule destruction and immunosuppression after repeated CpG oligodeoxynucleotide administration.","volume-title":"Nat. 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