Enhanced susceptibility of T lymphocytes to oxidative stress in the absence of the cellular prion protein

The cellular prion glycoprotein (PrPC) is ubiquitously expressed but its physiologic functions remain enigmatic, particularly in the immune system. Here, we demonstrate in vitro and in vivo that PrPC 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. PrPC 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 PrPC a protective function in thymocytes against oxidative stress.