The CD16−/CD56bright Subset of NK Cells Is Resistant to Oxidant-Induced Cell Death

Phagocyte-derived reactive oxygen species (“oxygen radicals”) have been ascribed a suppressive role in immunoregulation by inducing dysfunction and apoptotic cell death in lymphocytes. Earlier studies show that human NK cells are exceptionally sensitive to oxygen radical-induced apoptosis and functional inhibition. Two subsets of human CD56+ NK cells have been identified: the highly cytotoxic CD56dim cells which constitute >90% of NK cells in peripheral blood, and the less cytotoxic but efficiently cytokine-producing CD56bright cells. In this study, we demonstrate that the CD56bright subset of NK cells, in contrast to CD56dim cells, remains viable and functionally intact after exposure to phagocyte-derived or exogenously added oxygen radicals. The resistance of CD56bright cells to oxidative stress was accompanied by a high capacity of neutralizing exogenous hydrogen peroxide, and by a high cell-surface expression of antioxidative thiols. Our results imply that CD56bright NK cells are endowed with an efficient antioxidative defense system that protects them from oxygen radical-induced inactivation.