Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Faculty of Chemistry, Wroclaw University of Science and Technology, Wroclaw, Poland.
Lupus. 2020 Jun;29(7):705-714. doi: 10.1177/0961203320917749. Epub 2020 Apr 11.
Pathogenic CD4CD28 cells are characterized by inflammatory cytokine synthesis and tropism to the inflamed tissues. Recent studies showed the involvement of CD28 T cells in a severe clinical outcome of lupus. However, their role in moderately active disease is still unresolved.
We examined the levels of circulating CD4CD28 cells and CD8CD28 suppressor T cells. We also compared the CD4CD28 and CD4CD28 T-cell functional properties, including the expression of interferon gamma (IFN-γ) and Ki67 among systemic lupus erythematosus (SLE) patients ( = 20) and healthy controls ( = 20). All the patients were under immunosuppressive treatment and exhibited moderate SLE activity (median SLE Disease Activity Index (SLEDAI) = 6).
In patients, we found elevated CD4CD28 and unchanged levels of suppressor CD8CD28 T cells. There was no difference between patients and controls in IFN-γ and Ki67-expressing CD4, CD4CD28, and CD4CD28 T cells, except for higher IFN-γ levels in CD4CD28 T cells in SLE. In each studied group, we observed a higher preponderance of IFN-γ- and Ki67-expressing cells among CD4CD28 T cells and lower levels of IFN-γ in CD4CD28 T cells compared to the CD28+ subset. Similarly, Ki67 intensity was decreased in healthy CD4CD28 cells, whereas in patients, comparably high expression was observed in both subsets. IFN-γ intensity in CD4CD28 T cells correlated with SLEDAI.
SLE with a moderately active clinical course is characterized by peripheral blood expansion of CD4CD28 T cells and a normal abundance of suppressor CD8CD28 T cells. The demonstration that these pathogenic CD4 T cells, despite the lack of CD28, maintain the ability to produce pro-inflammatory IFN-γ positively correlated with disease activity as well as relatively high proliferative capacity may suggest their potentially predictive role in SLE flares.
致病性 CD4CD28 细胞的特征是炎症细胞因子的合成和对炎症组织的趋向性。最近的研究表明 CD28 T 细胞参与了狼疮的严重临床结局。然而，它们在中度活动疾病中的作用仍未解决。
我们检查了循环 CD4CD28 细胞和 CD8CD28 抑制性 T 细胞的水平。我们还比较了系统性红斑狼疮（SLE）患者（n=20）和健康对照者（n=20）中 CD4CD28 和 CD4CD28 T 细胞的功能特性，包括干扰素γ（IFN-γ）和 Ki67 的表达。所有患者均接受免疫抑制治疗，且表现为中度 SLE 活动（中位 SLE 疾病活动指数[SLEDAI] = 6）。
在患者中，我们发现 CD4CD28 升高，而抑制性 CD8CD28 T 细胞水平不变。SLE 患者和对照组之间，IFN-γ 和 Ki67 表达的 CD4、CD4CD28 和 CD4CD28 T 细胞没有差异，但 SLE 患者的 CD4CD28 T 细胞中 IFN-γ 水平更高。在每个研究组中，与 CD28+亚群相比，CD4CD28 T 细胞中 IFN-γ 和 Ki67 表达细胞的优势更高，而 CD4CD28 T 细胞中 IFN-γ 水平较低。同样，健康的 CD4CD28 细胞中 Ki67 强度降低，而患者的两个亚群中均观察到相当高的表达。CD4CD28 T 细胞中的 IFN-γ 强度与 SLEDAI 相关。
具有中度活动临床病程的 SLE 表现为外周血 CD4CD28 T 细胞的扩张和抑制性 CD8CD28 T 细胞的正常丰度。这些致病性 CD4 T 细胞尽管缺乏 CD28，但仍保持产生促炎 IFN-γ 的能力，且与疾病活动呈正相关，以及相对较高的增殖能力，这可能表明它们在 SLE 发作中具有潜在的预测作用。
