The X-linked chronic granulomatous disease (X-CGD), a rare genetic disease characterised by recurrent infections, is caused by mutations of NOX2. Significant proportions of X-CGD patients display signs of immune dysregulation. Regulatory T cells (Tregs) are CD4 lymphocytes that expand in active inflammation and prevent autoimmune disorders. Here we asked whether X-CGD is associated to Treg dysfunctions in adult patients. To this aim, the frequency of Tregs was analysed through intracellular flow cytometry in a cohort of adult X-CGD patients, carriers and controls. We found that Tregs were significantly expanded and activated in blood of adult X-CGD patients, and this was associated with activation of conventional CD4 cells (Tconvs). T cell activation was characterised by accumulation of intracellular ROS, not derived from NOX2 but likely produced by cellular metabolism. The higher TNF production by Tconvs in X-CGD patients might contribute to the expansion of Tregs through the TNFR2 receptor. In summary, our data indicate that Tregs expand in adult X-CGD in response to immune activation, and that the increase of NOX2-independent ROS content is a feature of activated T cells.

中文翻译：

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在成年 X-CGD 患者中，调节性 T 细胞扩增，而激活的 T 细胞则表现出不依赖于 NOX2 的 ROS 增加

X连锁慢性肉芽肿病（X-CGD）是一种以反复感染为特征的罕见遗传病，由NOX2突变引起。很大比例的 X-CGD 患者表现出免疫失调的迹象。调节性 T 细胞 (Treg) 是 CD4 淋巴细胞，可在活动性炎症中扩增并预防自身免疫性疾病。在这里，我们询问 X-CGD 是否与成年患者的 Treg 功能障碍有关。为此，通过细胞内流式细胞术对成年 X-CGD 患者、携带者和对照人群中的 Tregs 频率进行了分析。我们发现成人 X-CGD 患者血液中的 Tregs 显着扩增并激活，这与常规 CD4 细胞 (Tconv) 的激活有关。T 细胞激活的特点是细胞内 ROS 的积累，这些 ROS 并非源自 NOX2，而是可能由细胞代谢产生。X-CGD 患者中 Tconv 产生的 TNF 较高，可能有助于通过 TNFR2 受体扩增 Tregs。总之，我们的数据表明，Tregs 在成人 X-CGD 中响应免疫激活而扩增，并且不依赖于 NOX2 的 ROS 含量的增加是激活 T 细胞的一个特征。