系统性红斑狼疮骨髓T细胞活化及其与病情活动的相关性分析

目的 探讨系统性红斑狼疮（SLE）患者骨髓T淋巴细胞的活化状态及多种活化的T细胞亚群与疾病活动指标之间的相关性。方法 SLE患者11例（其中活动期6例，非活动期5例）和健康对照8名。应用流式细胞术比较活动期和非活动期SLE患者骨髓T细胞CD25、人类白细胞抗原（HLA）-DR的表达。用直线相关分析活化T细胞亚群与SLE疾病活动性评分（SLEDAI）、尿蛋白定量（24h）、血清补体C3、C4的相关性。结果 活动期SLE、非活动期SLE与正常对照相比骨髓T细胞CD25、HLA—DR的表达，差异均无统计学意义（P〉0．05）。活动期SLE骨髓T细胞HIJA—DR^＋、CD4^＋HLA—DR^＋、CD8^＋HLA—DR^＋的表达均明显高于正常对照外周血（P〈0．05）。11例SLE患者骨髓CD3^＋HLA—DR^＋、CD4^＋HLA—DR^＋细胞与C3之间均呈显著负相关（r=-0．682，r=-0．675，P均〈0．05）；CD3^＋HLA—DR^＋、CD8^＋-HLA—DR^＋细胞与尿蛋白定量（24h）之间均呈显著正相关（r=-0．712，r=-0．688，P均〈0．05）。活动期SLE骨髓CD3^＋HLA—DR^＋、CD8^＋HLA—DR^＋细胞与C3之间均呈显著负相关（r=-0．943，r=-0．829，P均〈0．05）。结论 活动期SLE患者骨髓T细胞活化明显高于正常对照外周血，且骨髓中活化的T细胞与疾病活动指标相关。     

外周血单核细胞CD69/CD3比值在评估系统性红斑狼疮疾病活动性中的作用

目的　通过检测系统性红斑狼疮 (SLE)患者外周血中T细胞CD6 9表达 ,以探讨CD6 9/CD3比值在评估SLE疾病活动指数中的作用。方法　利用流式细胞分析法对 5 4例SLE患者和 18名健康志愿者外周血T细胞上CD6 9表达进行分析 ,同时检测患者抗dsDNA抗体、C3和C4水平。结果　SLE患者CD6 9/CD3的比值显著高于正常人群 (P <0 0 1) ,当抗dsDNA抗体、C3和C4水平与疾病活动性缺乏相关关系时 ,CD6 9/CD3仍与SLE活动指数 (SLEDAI)有明显相关性 (P <0 0 5 )。结论　T细胞活化 (CD6 9/CD3)程度与SLEDAI指数有明显的相关性 ,可用于评估SLE疾病活动性     

外周血CD+4CD+25T细胞表达在系统性红斑狼疮患者中的意义

目的了解系统性红斑狼疮(SLE)患者外周血CD4 CD2 5T细胞表达及其临床意义。方法用流式细胞仪检测53例SLE患者外周血CD4 CD2 5T细胞表达,根据CD25表达荧光强度>100者为CD4 CD25brightT细胞,并与SLE活动指数评分(SLEDAI)、血清补体C3水平、抗双链DNA抗体、抗核抗体滴度进行相关分析。结果SLE患者外周血CD4 CD2 5T细胞表达率为(7·84±1·85)%,显著低于对照组(9·18±2·01)%(P<0·05),且活动期组[(6·72±1·16)%]较稳定期组更低[(8·57±1·91)%,P<0·01]。外周血CD4 CD25brightT细胞表达率在活动期组[(0·85±0·24)%]和稳定期组[(0·91±0·25)%]之间相比差异无统计学意义(P=0·686),但均低于对照组[(1·43±1·08)%,P<0·01]。随治疗后SLEDAI评分的下降,活动期组SLE患者外周血CD4 CD25brightT细胞表达率无明显变化。进一步分析外周血CD4 CD25brightT细胞表达率与SLEDAI评分、抗核抗体、抗双链DNA抗体滴度和血清C3水平的相关性,分别为ρ=-0·188,P=0·178;ρ=-0·216,P=0·121;ρ=0·082,P=0·560;ρ=0·010,P=0·944,差异均无统计学意义(P>0·05)。结论外周血CD4 CD2 5T细胞的减少可能与SLE的发病有关。     

系统性红斑狼疮T细胞活化及其与病情活动的相关性研究

目的探讨系统性红斑狼疮(SLE)患者T淋巴细胞的活化及多种活化的T细胞与疾病活动指标之间的相关性。方法SLE患者28例(其中活动期16例)和健康对照18名。应用流式细胞术,比较活动期和非活动期SLE患者外周血T细胞CD25、人类白细胞抗原(HLA)-DR以及CD69的表达差别。用直线相关分析判断活化T细胞与SLE疾病活动性评分(SLEDAI),24h尿蛋白定量,血清补体C3、C4的相关性。结果活动期SLE CD3~ CD69~ 和CD4~ CD25~ 细胞明显低于正常对照组(P＜0．05),CD3~ HLA-DR~ 、CD4~ HLA-DR~ 、CD8~ HLA-DR~ 细胞均明显高于正常对照组(P＜0．01),非活动期与正常对照组之间差异无统计学意义(P＞0．05)。28例SLE患者CD3~ CD69~ 细胞与SLEDAI评分、24h尿蛋白之间均呈显著负相关(r=-0．858,r=-0．756,P＜0．01),与CD4~ 细胞之间呈显著正相关(r=0．79,P＜0．01)。活动期SLE患者CD3~ CD69~ 细胞与C4、CD4~ 细胞之间均呈显著正相关(r=0．757,r=0．666,P＜0．05)。非活动期SLE患者CD3~ CD69~ 细胞与C3之间呈显著正相关,CD4~ HLA-DR~ 细胞与C4之间呈显著正相关,CD3~ HLA-DR~ 、CD8~ HLA-DR~ 细胞与CD4~ 细胞之间呈显著负相关(P＜0．05)。结论SLE患者活动期T淋巴细胞存在异常活化,SLE活动期CD3~ CD69~ 细胞数量减少,CD~3 CD69~ 细胞可以作为反映病情活动的指标。     

系统性红斑狼疮细胞与其病情活动性的相关性研究

目的 观察系统性红斑狼疮（SLE）患者外周血狼疮细胞（LEC）形态的变化，探讨其与SLE疾病活动性的关系。方法 采用经典改良血块法观察了50例SLE疾病活动期和30例SLE非活动期患者外周血LEC形态，同时与血清自身抗体、补体及SLE疾病活动指数（SLEDAI）对比研究。结果 特殊形态的LEC与自身抗体的抗dsDNA抗体和抗核小体抗体（AnuA）（r=0．588，P=0．056；r=0．759，P=0．135），补体C3和C4（r=-0．648，P=0．058；r=-0．589，P=0．057）及SLEDAI（r=0．686．P〈0．05）具有明显相关性。SLE活动期组特殊型LEC、自身抗体和补体与SLE非活动期组差异有统计学意义（P〈0．01）。当自身抗体和补体与SLEDAI无相关性时，特殊型LEC仍具有良好的相关性（r=0．786，P〈0．05）。结论 特殊型LEC与自身抗体、补体及SLEDAI有明显的相关性，可作为判断SLE疾病活动性的独特指标。     

系统性红斑狼疮患者T细胞上Fas受体分子与疾病活动指数的相关性研究

目的通过定量流式细胞术检测系统性红斑狼疮(SLE)患者T淋巴细胞表面Fas受体的分子数,探讨SLE的发病机制及与疾病活动指数的相关性.方法对36例活动期SLE患者和18名正常人群采集外周血,采用Fas定量流式细胞试剂盒荧光染色,通过流式细胞仪对T淋巴细胞上表达Fas受体分子数和凋亡率进行检测.结果活动期SLE患者T细胞表面表达Fas受体分子数和凋亡率较正常人群明显上调(P＜0.01).活动期SLE患者T细胞表面Fas受体分子数与T细胞凋亡率和SLEDAI之间,具有明显的正相关(P＜0.01),抗dsDNA抗体阳性患者组T细胞表面Fas受体分子数较抗dsDNA抗体阴性组明显增高,差异具有统计学意义(P＜0.05).结论SLE患者T淋巴细胞表面Fas受体分子数上调,由Fas介导的T淋巴细胞凋亡加快,刺激机体产生抗dsDNA等多种自身抗体,可能是引起SLE免疫功能紊乱的主要原因.SLE患者T淋巴细胞表面Fas受体分子数与SLE的活动性呈正相关,是一较好的评价SLE疾病活动性的指标.     

系统性红斑狼疮患者外周血CD4+CD25+FOXP3+调节性T细胞的检测和意义

目的检测系统性红斑狼疮（SEE）患者外周血CD4^＋CD25^＋FOXP3^＋调节性T细胞（Treg）的百分比，并分析其与疾病活动的相关性。方法采用流式细胞仪检测28例SLE患者（其中活动组18例）及22名正常对照组的外周血CD4^＋CD25^＋FOXP3^＋Treg的百分比，同时评估SLE疾病活动指数（SLEDAI）及检测血抗dsDNA水平，分析相关性。结果SLE患者外周血CD4^＋CD25^＋FOXP3^＋Treg占CD4^＋T细胞的百分比较对照组降低（P〈0．05），以活动组尤为明显，CD4^＋CD25^＋FOXP3^＋Treg的百分比与SLEDAI呈明显的负相关（P〈0．01），同时显示血抗dsDNA阳性组较阴性组患者外周血CD4^＋CD25^＋FOXP3^＋Treg的百分比显著下降（P〈0．01）。结论SLE患者外周血CD4^＋CD25^＋FOXP3^＋Treg的百分比在活动期下降为明显，其在SLE的发病机制中可能起到重要的作用。     

SLE活动期血清白蛋白、球蛋白比例变化的临床意义

检测28例系统性红斑狼疮（SLE）患者治疗前后的血清白蛋白（A）、球蛋白（G）、抗dsDNA、补体C3，观察上述指标在病情活动期与非活动期的差异及A／G比例与SLE疾病活动指数（SLEDAI）、抗dsDNA和补体C3的相关性；并与正常对照组比较。结果SLE活动期与非活动期、对照组比较，血清A、G、A／G比例、抗dsDNA、补体C3均有显著统计学差异（P〈0．01）；病程中A／G比例与SLEDAI、抗dsDNA和补体C3均相关，认为SLE活动期血清A／G比例显著性降低，能反映SLE病情变化。     

系统性红斑狼疮患者外周血CD4+CD25highFoxp3+调节性T细胞数量和Foxp3mRNA的表达水平与疾病活动性的相关性

目的 研究系统性红斑狼疮(SEE)患者CD4+CD25highFoxp3+调节性T细胞的数量及其功能基因Foxp3 mRNA的表达水平与SLE疾病活动性和肾脏损伤的相关性.方法 采用四色流式细胞术以Foxp3-异硫氰酸荧光素(FITC )/CD25-藻红蛋白/CD4-多甲藻叶绿素蛋白(PerCP)/CD3-藻蓝蛋白7抗体组合检测40名健康对照者及42例SLE患者外周血CD4+CD25highFoxp3+调节性T细胞的数量,实时荧光定量聚合酶链反应(PCR)检测特异性转录因子Foxp3 mRNA的表达水平,并分析其与SLE患者疾病活动指数(SLEDAI)、补体C3及血清抗双链DNA(dsDNA)抗体的关系.统计学方法采用t检验和Spearman相关分析.结果 活动期SLE患者外周血CD4+CD25highFoxp3+调节性T细胞数量显著低于健康对照组[(4±3)％与(7±4)％,P＜0.05],稳定期与健康对照组差异无统计学意义(P＞0.05);活动期SLE患者外周血CD4+CD25highFoxp3+调节性T细胞数量及CD4+CD25highFoxp3+调节性T细胞/CD4+比值显著低于稳定期患者[(4±3)％,(9±6)％与(5±4)％,(10±6)％,P均＜0.05];活动期SLE患者外周血Foxp3 mRNA的表达水平明显低于稳定期和对照组(P＜0.01,P＜0.05);SLE患者并发肾病组外周血CD4+CD25highFoxp3+调节性T细胞数量及CD4+CD25highFoxp3+调节性T细胞/CD4+比值显著低于SLE非肾病组(P＜0.05).相关分析显示,SLE患者外周血CD4+CD25highFoxp3+调节性T细胞数量与SLEDAI呈负相关(r=-0.5782,P＜0.05);CD4+CD25highFoxp3+调节性T细胞/CD4+比值与SLEDAI呈负相关(r=-0.4913,P＜0.05),与补体C3呈正相关(r=0.3687,P＜0.05);SLE患者外周血CD4+CD25highFoxp3+调节性T细胞数量与Foxp3 mRNA的表达水平呈正相关(r=0.6142,P＜0.0l).结论 SLE患者外周血CD4+CD25highFoxp3+调节性T细胞和Foxp3 mRNA的变化可能是导致SLE疾病发生和发展的关键因素之一,与疾病的活动性有密切关系.     

系统性红斑狼疮患者C1q受体和C1q抗体的表达及其与发病相关性的研究

目的 检测系统性红斑狼疮（SEE）患者外周血单个核细胞C1qRp和gC1qR的表达及与C1q抗体、补体C1q水平的关系，并进一步探讨其在SLE发病中的意义。方法 用流式细胞计数法测定58例SLE和30名正常人外周血中性粒细胞、单核细胞、淋巴细胞的C1qRp和gc1qR的表达，同时测血清C1q抗体、C1q水平．并将其与C3、c4、抗核抗体（ANA）、抗dsDNA抗体、SLEDAI积分做相关性分析。结果 SLE患者外周血中性粒细胞、单核细胞的C1qRp表达为（7．2±2-3）％和（3．4±2．1）％，均较正常人[（10．6±2．1）％和（9．0±8．7）％]降低（P〈0．05），淋巴细胞不表达C1qRp，但可表达gC1qR。C1qRp在SLE活动期表达略低于稳定期，但差异无统计学意义。SLE患者的gC1qR表达略高于正常人．gC1qR在活动期高于稳定期，但差异无统计学意义。SLE患者血清C1q抗体水平（98±41）U／ml，明显高于正常，C1q为（0．13±0．08）dE，低于正常值。外周血单个核细胞的C1qRp表达与血清C1qAb水平（Pearsonr=-0．574，P〈0．05）、双链DNA（ds—DNA）抗体滴度呈负相关，与补体C1q（Pearsonr=0．673．P〈0．01）、C3、C4水平呈正相关。gc1qR与C1qAb和补体C1q无明显相关性。结论 SLE患者外周血中性粒细胞、单个核细胞C1qR的表达缺陷，导致SLE吞噬功能受损，凋亡细胞清除障碍，诱导产生自身抗体，在SLE的免疫发病机制中起重要的作用。     

Roles of CCR2 and CXCR3 in the T cell-mediated response occurring during lupus flares

OBJECTIVE: Infiltrating lymphocytes have been demonstrated to play an important role in the tissue injury that occurs in systemic lupus erythematosus (SLE). Inflammatory chemokines control lymphocyte traffic through their interaction with T cell chemokine receptors. In this study we assessed the expression of chemokine receptors on T cell subsets of patients with active or inactive SLE. METHODS: Forty-four SLE patients (40 women and 4 men) were included in the study. The patients were divided according to their SLE Disease Activity Index (SLEDAI), which resulted in a group of patients with inactive SLE (n = 27) and a group with active SLE (n = 17). The control group was composed of 22 healthy blood donors. A disease control group consisted of 18 patients infected with human immunodeficiency virus. Expression of chemokine receptors CCR1, CCR2, CCR5, CXCR3, CXCR4, and CX3CR1 was assessed on whole blood samples by immunofluorescence analysis. RESULTS: On T lymphocytes, significant differences between the SLE patients and controls were observed only in the expression of CCR2 and CXCR3. On monocytes, no significant differences in CCR2 expression were observed between the healthy controls and the SLE patients. The proportion of CD8+,CCR2+ T cells was significantly lower in the SLE patients compared with the controls (mean +/- SD 2.3 +/- 1.3% and 3.5 +/- 3.2% in the active and inactive SLE groups, respectively, versus 21 +/- 24% in controls; P < 0.0001 for both). The CD4+,CCR2+ subset was represented similarly among the controls and patients with inactive SLE (16.7 +/- 5.8% and 12.8 +/- 8.1%, respectively) but was depleted in patients with active SLE (7.1 +/- 4.4%; P < 0.0001 versus controls). The active SLE group expressed significantly lower circulating levels of CD4+,CCR2+ T cells than did the inactive disease group (P = 0.007). A negative correlation was found between the proportion of CD4+,CCR2+ T cells and the SLEDAI (r = -0.43, P = 0.005, by Spearman's correlation). Proportions of CD8+,CXCR3+ T cells were similar between the SLE groups and the control group (58 +/- 22.6% in active SLE, 47.1 +/- 20% in inactive SLE, and 59.4 +/- 17.3% in controls). The proportion of CXCR3-expressing CD4+ T cells was decreased in the active disease group (23.5 +/- 3.2% versus 39.9 +/- 12.5% in controls; P = 0.008) but not in the inactive disease group (34.8 +/- 9.5%). A trend toward a significant negative correlation was observed between the decreased proportion of CD4+,CXCR3+ T cells and the SLEDAI (P = 0.08). Following in vitro activation of purified CD4 T cells, only CCR2 was internalized, whereas expression of CXCR3 was retained in activated CD4 cells. CONCLUSION: The numbers of circulating CD4+,CXCR3+ and CD4+,CCR2+ T cells are selectively decreased during SLE flares. A decrease in the number of circulating CD4+ T cells expressing CCR2 and/or CXCR3 could serve as a biomarker of the SLE flare.     

L-选择素在系统性红斑狼疮患者外周血CD4~+CD25~+T淋巴细胞的表达及其与Foxp3的相关性

目的了解黏附分子L-选择素(L-selectin,CD62L)在系统性红斑狼疮(systemic lupus erythematosus,SLE)患者外周血CD4+CD25+T淋巴细胞的表达,及其与CD4+CD25+Treg细胞转录因子Foxp3的相关性。方法用流式细胞仪检测68例SLE患者外周血CD4+、CD4+CD25+T淋巴细胞CD62L和Foxp3的表达。根据SLEDAI评分,68例SLE患者中活动组36例,稳定组32例;健康对照组35人。结果活动组SLE患者外周血CD4+CD25+CD62L+T淋巴细胞为(1.71±1.60)%,低于对照组的(5.87±3.03)%(P0.01)和稳定组的(4.91±1.69)%(P0.01),差异具有显著性意义;且与SLEDAI呈负相关(r=-0.695,P=0.000),与补体C3水平呈正相关(r=0.522,P=0.000)。活动组SLE患者外周血CD4+CD25+CD62L+Foxp3+T淋巴细胞为(1.06±0.47)%,低于对照组的(3.17±0.87)%(P0.01)和稳定组的(3.46±1.15)%(P0.01),差异有显著性意义。CD4+T淋巴细胞CD62L的表达与CD4+CD25+T淋巴细胞CD62L和Foxp3的表达呈负相关(r=-0.689,P=0.000;r=-0.568,P=0.000);CD4+CD25+T淋巴细胞CD62L的表达与Foxp3的表达呈正相关(r=0.891,P=0.000)。结论CD62L在SLE患者外周血CD4+CD25+T的低表达及与Foxp3表达密切相关,可能在SLE发病中起着重要作用。     

系统性红斑狼疮初发患者外周血T细胞免疫球蛋白及黏蛋白域蛋白-3及其配体半乳糖凝集素-9表达水平和意义

目的 通过检测T细胞免疫球蛋白及黏蛋白域蛋白(TIM)-3及其配体半乳糖凝集素-9在系统性红斑狼疮(SLE)初发患者外周血的表达水平,探讨其在SLE发病中的可能作用.方法 选取SLE初发患者33例,健康对照组26名,采用流式细胞术检测2组CD4+TIM-3+、CD8+TIM-3+细胞表达水平;实时荧光定量聚合酶链反应(PCR)技术比较2组外周血单个核细胞(PBMCs)半乳糖凝集素-9 mRNA表达水平;同时记录SLE组SLE疾病活动指数(SLEDAI)、补体C3水平和外周血淋巴细胞计数.两独立样本比较采用Mann-Whitney U检验;相关关系采用Spearman等级相关分析.结果 SLE组CD4+TIM-3+、CD8+TIM-3+细胞比率显著高于对照组(P＜0.01);其中CD4+TIM-3+、CD8+TIM-3+细胞数目与SLEDAI呈正相关(r=0.517,P＜0.01;=400,P＜0.05);与补体C3水平呈负相关(r=-0.487,P＜0.05;r=-0.395,P＜0.05).SLE组PBMCs半乳糖凝集素-9 mRNA表达较对照组显著上调(P＜0.05).结论 TIM-3-半乳糖凝集素-9通路可能参与了SLET细胞免疫调节,并与疾病活动性相关.

Abstract：

Objective To investigate the expression of T cell immunoglobulin domain and mucin domain (TIM)-3 and its ligand Galectin-9 in the peripheral blood of initial systemic lupus erythematosus (SLE)patients,and explore their effects on SLE.Methods The percentages of CD4+TIM-3+,CD8+TIM-3+cells from 33 SLE patients and 26 normal controls were detected by flow cytometry,and the Galectin-9 gene expression of PBMCs was determined by real-time PCR The SLE Disease Activity Index(SLEDAI),C3 level and lymphocyte count were evaluated.Mann-Whitney U test was used for independent samples analysis and Spearmen's test was used for correlation analysis.Results The percentages of CD4+TIM-3+ and CD8+TIM-3+ cells were markedly increased in SLE group than those of the control group(P<0.01).In particular,the CD4+TIM-3+,CD8+TIM-3+ level Was positively correlated with SLEDAI (r=0.517,P＜0.01;r=0.400,P＜0.05);but negatively correlated with C3(r=0.487,P＜0.05;r=0.395,P＜0.05).The Galectin-9 mRNA in SLE PBMCs was higher than that of the controls(P<0.05).Conclusion TIM-3-Galectin-9 pathway may be involved in T cell immune regulation of SLE,and is related to disease activity.     

系统性红斑狼疮患者CD4+CD25+调节性T细胞的变化

目的检测系统性红斑狼疮(SLE)患者外周血CD4 CD25 T细胞和CD4 CD25highT细胞占CD4 T细胞的比率,探讨其在SLE发病中的意义。方法采用流式细胞术检测93例SLE患者及47 名正常对照外周血CD4 CD25 调节性T细胞和CD4 CD25highT细胞占CD4 T细胞的比率,分析其与SLE 临床及实验室指标的关系。结果活动性SLE患者CD4 CD25 调节性T细胞及CD4 CD25highT细胞比例较正常人降低;CD4 CD25highT细胞水平与系统性红斑狼疮疾病活动指数(SLEDAI)呈负相关;CD4 CD25 调节性T细胞与抗核抗原抗体(ANA)、抗可提取的核抗原(ENA)抗体、抗dsDNA抗体、免疫球蛋白、补体C3、C4无相关。结论CD4 CD25 T细胞和CD4 CD25highT细胞可能参与SLE的发病机制。     

初发系统性红斑狼疮患者外周血CD4+调节性T细胞CD73表达

目的 研究CD73在初发活动性系统性红斑狼疮(SLE)患者外周血CD4+调节性T细胞的表达情况,探讨其在SLE发病中的作用.方法 采用流式细胞术检测29例初发未经治疗的活动期SLE患者(SLE组)和22例健康人(健康对照组)外周血CD4+CD25+CD73+T细胞百分率及CD4+CD73+、CD4+CDhi25、CD4+CD25+T细胞中叉头状转录因子3(FOXP3)蛋白表达,同时对CD73表达水平与SLE活动指标进行相关性分析.结果 SLE组患者外周血CD4+ CD25+ CD73+T细胞百分率低于健康对照组[(1.25±1. 32)%vs(2.35±1.09)%,P＜0.01].SLE组和健康正常对照组,CD73在C4+ CDhi25T细胞的表达水平[(29.05±12.53)%、(43.35±10.09)%]高于CD4+ CD25+T细胞[(17.48±6.92)%、(29.98±10.39)%,P＜0.001];FOXP3蛋白在CD4+ CD73+ T细胞[(65.36±14.40)%、(63.80±14.05)%]、CD4+ CDhi25 T细胞的表达水平[(67.30±13.04)%、(56.30±9.21)%]明显高于CD4+ CD25+ T细胞[(45.70±12.74)%、(43.98±5.17)%,P＜0.001],在CD4+ CD73-T细胞几乎不表达,而在CD4+ CD73+ T细胞、CD4+ CDhi25 T细胞中的表达差异无统计学意义(P值均大于0.05).CD73在CD4+ CD25+ T细胞的表达水平与SLE疾病活动指数、ESR、C反应蛋白、抗补体C1q、抗核小体抗体均无相关性(P＞0.05).结论 CD73可作为调节性T细胞新的表面标记,其在调节性T细胞中的异常表达可能参与SLE的发病机制.     

Roles of CCR2 and CXCR3 in the T cell–mediated response occurring during lupus flares

Objective

Infiltrating lymphocytes have been demonstrated to play an important role in the tissue injury that occurs in systemic lupus erythematosus (SLE). Inflammatory chemokines control lymphocyte traffic through their interaction with T cell chemokine receptors. In this study we assessed the expression of chemokine receptors on T cell subsets of patients with active or inactive SLE.

Methods

Forty‐four SLE patients (40 women and 4 men) were included in the study. The patients were divided according to their SLE Disease Activity Index (SLEDAI), which resulted in a group of patients with inactive SLE (n = 27) and a group with active SLE (n = 17). The control group was composed of 22 healthy blood donors. A disease control group consisted of 18 patients infected with human immunodeficiency virus. Expression of chemokine receptors CCR1, CCR2, CCR5, CXCR3, CXCR4, and CX3CR1 was assessed on whole blood samples by immunofluorescence analysis.

Results

On T lymphocytes, significant differences between the SLE patients and controls were observed only in the expression of CCR2 and CXCR3. On monocytes, no significant differences in CCR2 expression were observed between the healthy controls and the SLE patients. The proportion of CD8+,CCR2+ T cells was significantly lower in the SLE patients compared with the controls (mean ± SD 2.3 ± 1.3% and 3.5 ± 3.2% in the active and inactive SLE groups, respectively, versus 21 ± 24% in controls; P < 0.0001 for both). The CD4+,CCR2+ subset was represented similarly among the controls and patients with inactive SLE (16.7 ± 5.8% and 12.8 ± 8.1%, respectively) but was depleted in patients with active SLE (7.1 ± 4.4%; P < 0.0001 versus controls). The active SLE group expressed significantly lower circulating levels of CD4+,CCR2+ T cells than did the inactive disease group (P = 0.007). A negative correlation was found between the proportion of CD4+,CCR2+ T cells and the SLEDAI (r = −0.43, P = 0.005, by Spearman's correlation). Proportions of CD8+,CXCR3+ T cells were similar between the SLE groups and the control group (58 ± 22.6% in active SLE, 47.1 ± 20% in inactive SLE, and 59.4 ± 17.3% in controls). The proportion of CXCR3‐expressing CD4+ T cells was decreased in the active disease group (23.5 ± 3.2% versus 39.9 ± 12.5% in controls; P = 0.008) but not in the inactive disease group (34.8 ± 9.5%). A trend toward a significant negative correlation was observed between the decreased proportion of CD4+,CXCR3+ T cells and the SLEDAI (P = 0.08). Following in vitro activation of purified CD4 T cells, only CCR2 was internalized, whereas expression of CXCR3 was retained in activated CD4 cells.

Conclusion

The numbers of circulating CD4+,CXCR3+ and CD4+,CCR2+ T cells are selectively decreased during SLE flares. A decrease in the number of circulating CD4+ T cells expressing CCR2 and/or CXCR3 could serve as a biomarker of the SLE flare.

     

Increased Fas and Bcl-2 expression on peripheral mononuclear cells from patients with active juvenile-onset systemic lupus erythematosus

OBJECTIVE: To determine expressions of Fas and Bcl-2 on peripheral blood T and B lymphocytes from patients with juvenile-onset systemic lupus erythematosus (JSLE). METHODS: Thirty-eight patients with JSLE and 21 healthy controls were studied. Eleven JSLE patients with SLEDAI score >or= 8 were categorized as active. Freshly isolated peripheral blood mononuclear cells were stained for lymphocyte markers CD3, CD4, CD8, and CD19 and for Fas and Bcl-2 molecules. Cell protein expression was measured by 3-color flow cytometry. RESULTS: Percentages of lymphocytes positively stained for Fas antigen and cytoplasmic expression of Bcl-2 measured by mean fluorescence intensity from patients were significantly increased compared to controls on CD3+, CD4+, and CD8+ T cells. Patients with active disease had higher percentages of CD19+ B cells positive for Fas antigen compared to patients with inactive lupus. A direct statistical correlation was observed between Fas and Bcl-2 expression on CD19+ B cells and SLE Disease Activity Index score. CONCLUSION: Patients with juvenile-onset SLE show upregulation of apoptosis-related proteins. Patients with active and inactive disease have a different profile of Fas and Bcl-2 expression.