Thorén Fredrik B, Romero Ana I, Hermodsson Svante, Hellstrand Kristoffer
Department of Infectious Medicine, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
J Immunol. 2007 Jul 15;179(2):781-5. doi: 10.4049/jimmunol.179.2.781.
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 CD56(dim) cells which constitute >90% of NK cells in peripheral blood, and the less cytotoxic but efficiently cytokine-producing CD56(bright) cells. In this study, we demonstrate that the CD56(bright) subset of NK cells, in contrast to CD56(dim) cells, remains viable and functionally intact after exposure to phagocyte-derived or exogenously added oxygen radicals. The resistance of CD56(bright) 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 CD56(bright) NK cells are endowed with an efficient antioxidative defense system that protects them from oxygen radical-induced inactivation.
吞噬细胞衍生的活性氧（“氧自由基”）通过诱导淋巴细胞功能障碍和凋亡性细胞死亡，在免疫调节中发挥抑制作用。早期研究表明，人类自然杀伤细胞（NK细胞）对氧自由基诱导的凋亡和功能抑制异常敏感。已鉴定出人类CD56(+) NK细胞的两个亚群：高细胞毒性的CD56(dim)细胞，在外周血中占NK细胞的90%以上；细胞毒性较低但能高效产生细胞因子的CD56(bright)细胞。在本研究中，我们证明，与CD56(dim)细胞相比，NK细胞的CD56(bright)亚群在暴露于吞噬细胞衍生的或外源性添加的氧自由基后仍能存活且功能完整。CD56(bright)细胞对氧化应激的抗性伴随着中和外源性过氧化氢的高能力，以及抗氧化硫醇在细胞表面的高表达。我们的结果表明，CD56(bright) NK细胞具有高效的抗氧化防御系统，可保护它们免受氧自由基诱导的失活。
