文章摘要
徐安琪,杨晓帆,王慧娟,张缪佳,季晓辉.系统性红斑狼疮患者外周血T细胞CTLA-4表达及其临床意义[J].南京医科大学学报,2017,(1):62~68
系统性红斑狼疮患者外周血T细胞CTLA-4表达及其临床意义
Expression of CTLA-4 in T cells from peripheral blood of patients with systemic lupus erythematosus and its clinical significance
投稿时间:2016-07-03  
DOI:10.7655/NYDXBNS20170113
中文关键词: 系统性红斑狼疮  T细胞  CTLA-4
英文关键词: systemic lupus erythematosus  T cells  CTLA-4
基金项目:南京医科大学科技发展基金项目资助(NY020609)
作者单位
徐安琪 南京红十字血液中心研究室江苏 南京 210003 
杨晓帆 南京医科大学基础医学院免疫学系江苏 南京 211166 
王慧娟 南京医科大学基础医学院免疫学系江苏 南京 211166 
张缪佳 南京医科大学第一附属医院风湿病科江苏 南京 210029 
季晓辉 南京医科大学基础医学院免疫学系江苏 南京 211166 
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中文摘要:
      目的:研究系统性红斑狼疮(systemic lupus erythematosus, SLE)T细胞中CTLA-4的表达及临床意义。方法:分离正常人和SLE患者的外周血单个核细胞(peripheral blood mononuclear cells,PBMCs),以抗-CD3、抗-CD28刺激培养48 h,刺激培养前后收取细胞,以流式细胞术(FCM)检测CD4+和CD8+T细胞中CTLA-4+细胞比例,并分析其与SLE疾病活动性指数(SLEDAI)和肾损害的关系。再以ELISA法检测培养上清中游离的CTLA-4水平。结果:SLE患者刺激前的CD4+和CD8+T细胞且主要是CD25+T细胞中CTLA-4+细胞的比例较正常人显著增高,与SLEDAI呈正相关;而其CD8+CD28- T细胞中CTLA-4+细胞比例也显著高于正常人,但与SLEDAI之间无显著相关性;经抗-CD3、抗-CD28抗体刺激后,其CD4+CD25+T细胞、CD8+CD25+T细胞或CD8+CD28-T细胞中CTLA-4+细胞的比例却显著低于正常人,但与SLEDAI之间无显著相关性,仅在活动性SLE患者中有肾损组的CD8+CD28-T细胞中CTLA-4+细胞的比例显著低于非肾损组;而且经刺激培养后SLE患者PBMC上清中游离的CTLA-4水平也显著低于正常人。结论:SLE患者新鲜分离的T细胞(CD4+及CD8+)中CTLA-4表达异常增高,反映T细胞异常活化和疾病活动;另一方面,SLE患者T细胞又存在CTLA-4诱导性表达障碍,可能与SLE T细胞体外再活化能力减弱有关。
英文摘要:
      Objective: To investigate CTLA-4 expression in T cells from peripheral blood of patients with systemic lupus erythematosus (SLE) and its significance in clinic. Methods: Peripheral blood mononuclear cells (PBMCs) from SLE patients and healthy donors were isolated and then cultured with anti-CD3 and anti-CD28 antibodies for 48 hours. Before and after culture, the cells were detected for the percentages of CTLA-4+ cells in CD4+ and CD8+ T subsets by flow cytometry (FCM). Based on these data, the correlation between CTLA-4 expression in CD4+ or CD8+ T subsets of SLE patients and SLE disease activity index (SLEDAI) and kidney damage were analyzed. Cell culture supernatants were also collected for the determination of free CTLA-4 level by ELISA. Results: In fresh PBMC, CTLA-4+ cell percentages of CD4+CD25+ and CD8+CD25+ T subsets in SLE patients, were significantly higher than those in controls, and were positively correlated with SLEDAI; CTLA-4+ cell percentage of CD8+CD28- T subset was also significantly higher in SLE than that in controls, but was not correlated with SLEDAI. After stimulation with anti-CD3 and anti-CD28, CTLA-4+ percentages of CD4+CD25+, CD8+CD25+ and CD8+CD28- T subsets were significantly lower in SLE than those in controls, but was not correlated with SLEDAI. While in active SLE, CTLA-4+ cell percentage of CD8+CD28- T subsets was significantly lower in patients with kidney damage than that in patients without kidney damage; CTLA-4 level of the culture supernatant was lower in SLE patients than that in controls. Conclusion: The abnormally increased expression of CTLA-4 in T (CD4+ and CD8+) cells fresh isolated from SLE patients T cells might indicate disease development with T cell activation. On the other hand, T cells of SLE patients are deficient in induced expression of CTLA-4, which might be related with the deficient ability of reactivation of SLE T cells in vitro.
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