title: Overexpression of cellular prion protein induces an antioxidant environment altering T cell development in the thymus.
abstract: Cellular prion protein (PrP(C)) is an ubiquitously expressed glycoprotein whose roles are still widely discussed, particularly in the field of immunology. Using TgA20- and Tg33-transgenic mice overexpressing PrP(C), we investigated the consequences of this overexpression on T cell development. In both models, overexpression of PrP(C) induces strong alterations at different steps of T cell maturation. On TgA20 mice, we observed that these alterations are cell autonomous and lead to a decrease of alphabeta T cells and a concomitant increase of gammadelta T cell numbers. PrP(C) has been shown to bind and chelate copper and, interestingly, under a copper supplementation diet, TgA20 mice presented a partial restoration of the alphabeta T cell development, suggesting that PrP(C) overexpression, by chelating copper, generates an antioxidant context differentially impacting on alphabeta and gammadelta T cell lineage.
authors.affiliation: Laboratoire d'Immunochimie, Commissariat à l'Energie Atomique, Institut National de la Santé et de la Recherche Médicale Unité 548, Université J. Fourier, 17 Rue des Martyrs, 38054 Grenoble, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Jouvin-Marche
authors.forename: Valérie
authors.initials: V
authors.lastname: Attuil-Audenis
authors.forename: Catherine
authors.initials: C
authors.lastname: Aude-Garcia
authors.forename: Walid
authors.initials: W
authors.lastname: Rachidi
authors.forename: Mark
authors.initials: M
authors.lastname: Zabel
authors.forename: Valérie
authors.initials: V
authors.lastname: Podevin-Dimster
authors.forename: Carole
authors.initials: C
authors.lastname: Siret
authors.forename: Christoph
authors.initials: C
authors.lastname: Huber
authors.forename: Marianne
authors.initials: M
authors.lastname: Martinic
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Riondel
authors.forename: Christian L
authors.initials: CL
authors.lastname: Villiers
authors.forename: Alain
authors.initials: A
authors.lastname: Favier
authors.forename: Philippe
authors.initials: P
authors.lastname: Naquet
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Cesbron
authors.forename: Patrice N
authors.initials: PN
authors.lastname: Marche
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000975:Antioxidants / Q000378:metabolism*; D002454:Cell Differentiation; D003300:Copper / Q000494:pharmacology; D019587:Dietary Supplements; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D000975:Antioxidants; D011328:Prions; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003300:Copper