摘要
目的:研究与系统性红斑狼疮(systemic lupus erythematosus,SLE)病理活动相关的调节性T细胞(regulatory T cell,Treg)标志。方法:分离正常人和SLE患者外周血单个核细胞(PBMCs),用三色流式细胞术(flowcytometer,FCM)检测CD4和CD8 T细胞亚群的CD25、Foxp3表达,分析T细胞Foxp3+/CD4+T、CD25+Foxp3+/CD4+、Foxp3+/CD4+CD25+、Foxp3+/CD8+、CD25+Foxp3+/CD8+、及Foxp3+/CD8+CD25+的比值变化,及其与SLE疾病活动指数(SLE disease activity index,SLEDAI)、抗-dsDNA阳性、补体C3/C4水平降低、血清IgG水平增高、肾脏损害、关节病变、白细胞减少、疾病初/复发的关系。结果:①与正常人相比,SLE患者T细胞CD4+CD25+/CD4+比值无明显改变,但中/重度SLE患者外周血T细胞Foxp3+/CD4+、CD25+Foxp3+/CD4+、及Foxp3+/CD4+CD25+比值均显著下降,并与SLEDAI呈负相关;其中CD25+Foxp3+/CD4+比值还与SLE的抗-dsDNA阳性、补体C3/C4水平降低、血清IgG水平增高相关,在疾病初发、肾脏损害、白细胞减少患者该比值下降更为显著;②SLE患者CD8+T细胞中CD25+、Foxp3+亚群比例未见明显减少,仅中/重度活动性SLE患者Foxp3+/CD8+CD25+比例减少,但与SLEDAI无相关性。结论:以CD25+Foxp3+作为Treg标志,可以明显反映出SLE患者CD4+Treg存在数量缺陷,并与疾病活动性、免疫功能紊乱和病理损害密切相关,故将CD4+CD25+Foxp3+作为标志进行Treg检测对辨明SLE患者免疫系统功能状态具有一定的临床参考价值。
Objective:To investigate markers of regulatory T cells in the pathogenesis of systemic lupus erythematosus (SLE). Methods:Peripheral blood mononuelear cells (PBMCs) were isolated from SLE patients and healthy donors;Flow cytometry (FCS) was used to detect the expressions of CD25 and Foxp3 in CD4 and CD8 T subsets and analyze the changes in the ratios of Foxp3+/ CD4+,CD25+F+xp3+/CD4+F+xp3+/CD4+CD25+,F+xp3+/CD8+CD25+F+xp3+/CD8+F+xp3+/CD8+CD25+,and their relationships with SLEDAI, anti-dsDNA antibodies, complement C3/C4, serum IgG, kidney damage and leucopenia. Results: ①Compared with healthy donors,the percentage of CD25+ cells in CD4+T cells did not change significantly in SLE patients,but the ratios of Foxp3+/CD4+, CD25+Foxp3+/CD4+ and Foxp3+/CD4+CD25+ significantly reduced in patients with mid- and high-active SLE, and the ratios were also negatively correlated to SLEDAI. Particularly,the ratio of CD25+Foxp3+/CD4+ in SLE patients was related with anti-dsDNA antibody, decrease of complement C3/C4 and increase of IgG;and the reduce of CD25+Foxp3+/CD4+ ratio was remarkable in SLE patients with renal damage or Leucopenia and patients in initial disease stage. ② Foxp3+ cells ratio of CD8+ cell population was similar between SLE patients and healthy controls,except that the ratio of Foxp3+/CD8+CD25+ decresed in mid- and high-active SLE patients, but had no relationship with disease activity. Conclusion:CD4+CD25+Foxp3+ is an important marker for evaluation of regulatory T cells, which reflects the deficient quantity of Treg, and might reflects the deficient function of Treg by the relationship between the cell percentage and SLE disease activity,immune disorder and tissue lesion. The study confirmed that CD4+CD25+Foxp3 + as the marker of Treg is significant for evaluation of immune system functional status of SLE patients in clinical.
出处
《南京医科大学学报(自然科学版)》
CAS
CSCD
北大核心
2012年第6期745-753,共9页
Journal of Nanjing Medical University(Natural Sciences)
基金
南京医科大学科技发展基金资助(NY020609)