Enhanced susceptibility of T lymphocytes to oxidative stress in the absence of the cellular prion protein.
The cellular prion glycoprotein (PrP(C)) is ubiquitously expressed but its physiologic functions remain enigmatic, particularly in the immune system. Here, we demonstrate in vitro and in vivo that PrP(C) is involved in T lymphocytes response to oxidative stress. By monitoring the intracellular level of reduced glutathione, we show that PrP(-/-) thymocytes display a higher susceptibility to H(2)O(2) exposure than PrP(+/+) cells. Furthermore, we find that in mice fed with a restricted diet, a regimen known to increase the intracellular level of ROS, PrP(-/-) thymocytes are more sensitive to oxidative stress. PrP(C) function appears to be specific for oxidative stress, since no significant differences are observed between PrP(-/-) and PrP(+/+) mice exposed to other kinds of stress. We also show a marked evolution of the redox status of T cells throughout differentiation in the thymus. Taken together, our results clearly ascribe to PrP(C) a protective function in thymocytes against oxidative stress.
Aude-Garcia
Catherine
C
CEA, DSV, iRTSV, Laboratoire Biochimie et Biophysique des Systèmes Intégrés, 17 rue des Martyrs, 38054, Grenoble Cedex 9, France. catherine.aude-garcia@cea.fr
Villiers
Christian
C
Candéias
Serge M
SM
Garrel
Catherine
C
Bertrand
Caroline
C
Collin
Véronique
V
Marche
Patrice N
PN
Jouvin-Marche
Evelyne
E
D000818:Animals; D002478:Cells, Cultured; D017353:Gene Deletion; D005978:Glutathione / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
D011328:Prions; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D005978:Glutathione