Overexpression of cellular prion protein induces an antioxidant environment altering T cell development in the thymus.
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.
Jouvin-Marche
Evelyne
E
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.
Attuil-Audenis
Valérie
V
Aude-Garcia
Catherine
C
Rachidi
Walid
W
Zabel
Mark
M
Podevin-Dimster
Valérie
V
Siret
Carole
C
Huber
Christoph
C
Martinic
Marianne
M
Riondel
Jacqueline
J
Villiers
Christian L
CL
Favier
Alain
A
Naquet
Philippe
P
Cesbron
Jean-Yves
JY
Marche
Patrice N
PN
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*
D015703:Antigens, CD; D000975:Antioxidants; D011328:Prions; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003300:Copper