Yang Xiaofan, Wang Weiwen, Xu Juan, Zhang Ming-Shun, Mei Huanping, Shen Youxuan, Zhang Miao-Jia, Ji Xiaohui, Wang Huijuan
Department of Immunology, School of Basic Medical Science, Nanjing Medical University (NJMU), Nanjing 211166, China.
Nanjing First Hospital Affiliated to NJMU, Nanjing 210006, China.
Ann Transl Med. 2019 Mar;7(5):93. doi: 10.21037/atm.2019.01.38.
Regulatory T (Treg) cells are one of the important mechanisms in maintaining self-tolerance and immune homeostasis. CD4CD25Foxp3Treg is considered to have a role in the pathogenesis of systemic lupus erythematosus (SLE). However, the data reported is controversial, and a conclusive result has not been given thus far. The aim of the present study is to evaluate the role of CD4Treg in SLE further.
The peripheral blood T cells (PBMCs) from patients with SLE and healthy controls were isolated, and followed by the isolation of CD3T cells. The PBMCs were tested for the expressions of CD25 and Foxp3 molecules on the surface of CD4T cells, and CD3T cells were tested for their cytokine expressions including IFN-γ, TGF-β, and IL-10, with the method of flow cytometry. The correlations of test results with clinical features of the disease were evaluated by linear correlation analysis.
CD4CD25 Foxp3Treg decreased in SLE patients and was correlated with the SLE Disease Activity Index (SLEDAI), and a few immunological abnormalities, including anti-dsDNA antibody positive, IgG increase and C3 decrease, and types of tissue damage, including leukocytopenia and kidney damage. IFN-γ cells in the CD4CD25T subset fresh-isolated from SLE patients increased slightly, but IFN-γ-producing response to stimulation in CD4CD25T subset of SLE decreased. The number of TGF-β-producing cells in the CD4CD25T subset from SLE patients also decreased. While the percentages of CD4CD25IL-10T subset in the CD3T cells increased in SLE, however, these changes of cytokine expressions did not show any significant correlations with SLEDAI.
There is clear and definite evidence from the present study indicating the important role of CD4CD25Foxp3Treg in the pathogenesis of SLE, for the abnormalities in functional cytokine productions of the CD4CD25 T subset, and for the feasibility of a CD4CD25Foxp3Treg- based immunotherapy in SLE.
调节性T(Treg)细胞是维持自身耐受和免疫稳态的重要机制之一。CD4⁺CD25⁺Foxp3⁺ Treg被认为在系统性红斑狼疮(SLE)的发病机制中起作用。然而,所报道的数据存在争议,迄今为止尚未得出确凿结果。本研究的目的是进一步评估CD4⁺Treg在SLE中的作用。
分离SLE患者和健康对照者的外周血T细胞(PBMCs),随后分离CD3⁺T细胞。采用流式细胞术检测PBMCs中CD4⁺T细胞表面CD25和Foxp3分子的表达,检测CD3⁺T细胞细胞因子IFN-γ、TGF-β和IL-10的表达。通过线性相关分析评估检测结果与疾病临床特征的相关性。
SLE患者CD4⁺CD25⁺ Foxp3⁺Treg减少,且与SLE疾病活动指数(SLEDAI)相关,还与一些免疫异常相关,包括抗双链DNA抗体阳性、IgG升高和C3降低,以及与包括白细胞减少和肾脏损害在内的组织损伤类型相关。从SLE患者新鲜分离的CD4⁺CD25⁻T亚群中的IFN-γ细胞略有增加,但SLE患者CD4⁺CD25⁻T亚群对刺激产生IFN-γ的反应降低。SLE患者CD4⁺CD25⁺T亚群中产生TGF-β的细胞数量也减少。虽然SLE患者CD3⁺T细胞中CD4⁺CD25⁺IL-10⁺T亚群的百分比增加,然而,这些细胞因子表达的变化与SLEDAI均无显著相关性。
本研究有明确证据表明CD4⁺CD25⁺Foxp3⁺Treg在SLE发病机制中起重要作用,CD4⁺CD25⁻T亚群功能性细胞因子产生异常,以及基于CD4⁺CD25⁺Foxp3⁺Treg的免疫疗法在SLE中的可行性。