1 Department of Rheumatology, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing, China.
2 Department of Immunology, School of Basic Medical Science, Nanjing Medical University, Nanjing, China.
Lupus. 2019 Sep;28(10):1214-1223. doi: 10.1177/0961203319867130. Epub 2019 Aug 9.
The aim of this study was to evaluate the changes in CD8CD28/CD8CD28 T-cell subset balance and in the CD8CD28 Treg cell number and function in patients with systemic lupus erythematosus (SLE).
Cell isolation and flow cytometry analysis were employed to investigate the T-cell subsets.
It was found that in high-activity SLE patients, the CD8CD28 T-cell subset was reduced, which was inversely correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and that the CD8CD28/CD8CD28 ratio was elevated, which was positively correlated with SLEDAI and with renal damage and inversely correlated with serum complement level, whereas the CD8CD28 T-cell subset was increased only in inactive patients. It was also found that apoptosis of CD8 T cells increased, and Fas, Fas ligand (FasL) and interleukin (IL)-6 expression were high, whereas cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) expression was low by the CD8CD28 T cell subset in active SLE patients; apoptosis was positively correlated with SLEDAI and with the expression of Fas and FasL by the CD8CD28 T-cell subset in active SLE patients. IL-6 and CTLA-4 expression were found to be low by the CD8CD28 T cell subset in active SLE patients.
These data suggest that high expression of Fas, FasL and IL-6 and low expression of CTLA-4 by the CD8CD28 T-cell subset promotes the activation-induced cell death of the CD8CD28 T-cell subset, resulting in an imbalance of CD8CD28/CD8CD28 T cells in active SLE patients, which represents an important feature in the immunological pathogenesis of SLE. The CD8CD28 T-cell subset may play some role in inactive SLE.
本研究旨在评估 CD8CD28/CD8CD28 T 细胞亚群平衡及 CD8CD28 Treg 细胞数量和功能在系统性红斑狼疮（SLE）患者中的变化。
采用细胞分离和流式细胞术分析来研究 T 细胞亚群。
研究发现，在高活动度 SLE 患者中，CD8CD28 T 细胞亚群减少，与系统性红斑狼疮疾病活动指数（SLEDAI）呈负相关，而 CD8CD28/CD8CD28 比值升高，与 SLEDAI 及肾损害呈正相关，与血清补体水平呈负相关，而 CD8CD28 T 细胞亚群仅在非活动患者中增加。还发现，CD8 T 细胞凋亡增加，Fas、Fas 配体（FasL）和白细胞介素（IL）-6 表达增高，而细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）表达降低，在活动期 SLE 患者的 CD8CD28 T 细胞亚群中；凋亡与 SLEDAI 呈正相关，与 Fas 和 FasL 在活动期 SLE 患者的 CD8CD28 T 细胞亚群中的表达呈正相关。在活动期 SLE 患者的 CD8CD28 T 细胞亚群中发现 IL-6 和 CTLA-4 表达降低。
这些数据表明，CD8CD28 T 细胞亚群中 Fas、FasL 和 IL-6 高表达及 CTLA-4 低表达促进 CD8CD28 T 细胞亚群的激活诱导细胞死亡，导致活动期 SLE 患者 CD8CD28/CD8CD28 T 细胞失衡，这是 SLE 免疫发病机制的一个重要特征。CD8CD28 T 细胞亚群可能在非活动期 SLE 中发挥一定作用。
