Naturally occurring regulatory T cells show reduced sensitivity toward oxidative stress-induced cell death
Naturally occurring regulatory T cells show reduced sensitivity toward oxidative stress-induced cell death
复制标题
DOI：
10.1182/blood-2008-09-181040
复制
发表时间：
2009-04-09
期刊：
影响因子：
20.3
通讯作者：
Kiessling, Rolf
中科院分区：
文献类型：
--
作者：
Mougiakakos, Dimitrios;Johansson, C. Christian;Kiessling, Rolf
尽管几项研究的作者报告了血液和实体恶性肿瘤中免疫抑制调节性T细胞（Tcells）数量的升高，但其潜在机制尚未完全阐明。癌症与通过恶性细胞、粒细胞、肿瘤相关巨噬细胞和髓源性抑制细胞产生的活性氧介导的氧化应激相关。已知氧化应激在慢性炎症和癌症期间对自然杀伤细胞（NK）和T细胞具有有害影响。巧合的是，在肿瘤部位可以检测到更大数量的TcR，表明TcR可以在这种氧化应激增加的环境中持续存在。我们证明，T细胞，特别是幼稚的CD 45 RA（+），表现出降低敏感性氧化应激诱导的细胞死亡，并保持其抑制功能，这可能是由于其观察到的高抗氧化能力的现象。这种新描述的特征可以解释它们在与氧化应激水平增加相关的恶性肿瘤中的富集。（血。2009; 113：3542-3545）
Although the authors of several studies report elevated numbers of immunosuppressive regulatory T cells (Tregs) in hematologic and solid malignancies, the underlying mechanism is not fully clarified. Cancer is associated with oxidative stress mediated through reactive oxygen species produced by malignant cells, granulocytes, tumor-associated macrophages, and myeloid-derived suppressor cells. Oxidative stress is known to have detrimental effects on natural killer (NK) and T cells during chronic inflammatory conditions and cancer. Paradoxically, greater numbers of Tregs can be detected at tumor sites, indicating that Tregs can persist in this environment of increased oxidative stress. We demonstrate that Tregs, especially naive CD45RA(+), exhibit reduced sensitivity to oxidative stress-induced cell death and maintain their suppressive function, a phenomenon that may be attributed to their observed high antioxidative capacity. This newly described characteristic could explain their enrichment in malignancies associated with increased levels of oxidative stress. (Blood. 2009; 113: 3542-3545)