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 H₂O₂ 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.