Abstract
Abstract During an infection or carcinogenesis, the stimulation of immune cells may lead to elevated intracellular levels of reactive oxygen species (ROS), and this oxidative stress can cause damage to the cell. Interestingly, previous reports have shown that ROS produced through cell activation play a critical role as signaling messengers in immune responses. Yet, little is known in regard to the role of ROS in natural killer (NK) cell effector functions. Our data suggest that the levels of ROS increase in NK cells upon stimulation. Therefore, we hypothesize that, upon stimulation of NK cells, ROS accumulate and provide positive signaling that leads to the upregulation of NK cell effector functions. To test this hypothesis, we examined NK cell function and proliferation in Glrx2-deficient mice in which the ROS levels are elevated in the mitochondrial matrix due to a defect in the redox system. We found that lack of Glrx2 in NK and T cells does not improve their cytotoxic potential or their ability to produce IFNg. However, Glrx2-deficient NK cells showed enhanced proliferation when stimulated with IL-2, indicating that during prolonged stress, the elevated levels of ROS drive NK cells to undergo robust cell division. This finding will elucidate a link between the levels of ROS and immune cell proliferation during viral infection and carcinogenesis.