系统性红斑狼疮患者外周血CD4+CD25+T细胞亚群的初步研究

目的研究系统性红斑狼疮(SLE)患者外周血中CD4+CD25+T细胞亚群的比率改变.方法采用微量全血三色标记法,以流式细胞技术检测SLE患者外周血CD4+、CD4+CD25+、CD4+CD25+CD45RO+T细胞亚群,分析阳性细胞百分率和平均荧光强度(Mean fluorescence intensity,MFI).结果SLE患者外周血中CD4+T细胞百分率,活动期(29.29%±8.86)%和非活动期(29.55±8.96)%均低于正常对照(37.41±3.29)%(P均＜0.05);CD4+CD25+T细胞百分率SLE活动期(10.30±5.60)%显著高于正常对照(5.39±1.43)%(P＜0.05),非活动性SLE病人组(5.63±2.49)%和正常组差异无显著性(P＞0.05);CD4+CD25+CD45RO+T细胞百分率SLE活动期(3.96±3.51)%显著高于正常对照(1.39±0.63)%,非活动期(0.75±0.66)%显著低于正常对照(P均＜0.05).平均荧光强度分析表明SLE患者组和正常组的CD25和CD45RO抗原密度差异并无显著性(P均＞0.05).结论SLE患者外周血中存在CD4+CD25+及CD4+CD25+CD45RO+T细胞亚群比率异常增高,且与病情活动性相关.     

趋化因子及其受体表达与系统性红斑狼疮临床特征相关性研究

目的研究趋化因子及受体变化与系统性红斑狼疮(SLE)临床特征的相关性。方法采用ELISA法检测37例初发SLE患者和20例正常对照的巨噬细胞炎症蛋白(MIP)-1α、巨噬细胞炎症蛋白(MIP)-1β、激活正常T细胞表达和分泌因子(RANTES)的血清水平,用流式细胞术检测其中18例初发SLE患者及10例正常对照外周血CD4+T细胞表面趋化因子受体CCR1、CCR3、CCR5的表达情况,分析它们的变化与不同临床特征的相关性。结果SLE伴发热患者血清MIP-1α浓度为(52±27)ng/L,体温正常的SLE患者为(28±19)ng/L,差异有统计学意义(P<0·01);SLE伴关节炎患者血清MIP-1β浓度为(221±158)ng/L,不伴关节炎患者为(95±83)ng/L,差异有统计学意义(P<0·01);血清RANTES浓度在血小板减少的SLE患者中为(130±122)ng/L,血小板正常患者为(212±114)ng/L,差异有统计学意义(P<0·05);抗RNP抗体阳性的SLE患者外周血CD4+T细胞中CD4+CCR3+细胞亚群百分率为(14·8±3·0)%,抗RNP抗体阴性患者为(11·3±2·6)%,差异有统计学意义(P<0·05)。结论不同的趋化因子及受体表达异常可能与系统性红斑狼疮系统不同临床特征有关。     

活动期系统性红斑狼疮患者T细胞亚群分布和活化

目的探讨T细胞亚群分布的紊乱及其活化异常在系统性红班狼疮(SLE)发病中的作用.方法用流式细胞仪检测18例活动期SLE患者和50例正常人外周血中CD4 、CD8 、CD4 CD25 及CD8 CD25 T细胞的百分率及相互之间的比率,并进行统计学处理.结果活动期SLE患者外周血中CD8 T细胞百分率明显升高(P＜0.01),CD4 /CD8 比率降低(P＜0.05);CD8 CD25 T细胞的百分率降低(P＜0.01),CD4 CD25 /CD8 CD25 比率明显升高(P＜0.01);CD4 T细胞和CD4 CD25 T细胞百分率无明显改变(P＞0.05);而这些指标与SLE疾病活动性评分指数(SLEDAI)均无相关性.结论活动期SLE患者同时存在T细胞CD4 、CD8 亚群分布和活化的异常,导致T细胞功能紊乱,可能是SLE的重要致病机制之一.     

小鼠骨髓间充质干细胞调节T细胞亚群表达趋化因子受体的研究

目的:研究小鼠T淋巴细胞亚群受骨髓间充质干细胞(mesenchymal stem cells,MSCs)调控表达趋化因子受体的变化。方法:小鼠骨髓细胞悬液进行贴壁培养法分离出骨髓间充质干细胞,经培养扩增后按不同比例(10%及1%)与经过植物血凝素(PHA)刺激的小鼠淋巴细胞混合培养,流式细胞术检测趋化因子受体CXCR3,CCR5,CCR7在不同T细胞亚群中表达的变化。结果:在CD3+CD8+亚群中,添加了骨髓间充质干细胞的两个培养组均较对照组增高表达CXCR3及CCR7(P0.05),而CCR5仅在10%MSC的高浓度组较对照组有增高表达。在CD3+CD4+亚群中,CXCR3的表达在10%MSC组、1%MSC组及对照组表达差异均无统计学意义(P0.05);CCR5及CCR7在添加了骨髓间充质干细胞的两个培养组均较对照组增高表达,且在该两种骨髓间充质干细胞浓度梯度中呈剂量依赖性。结论:骨髓间充质干细胞在与淋巴细胞呈一定的细胞比例共培养时能不同程度上调T淋巴细胞及亚群表达趋化因子受体CXCR3、CCR5、CCR7,提示骨髓间充质干细胞可提高T淋巴细胞亚群的趋化能力。     

不同期别梅毒患者外周血CD4~+T细胞表面趋化因子受体的研究

目的探讨不同期别梅毒患者外周血CD4~+T细胞表面趋化因子受体的水平。方法选取我院2014年2月-2016年9月收治的梅毒患者,检测不同期别梅毒患者的外周血CD4~+T细胞表面趋化因子受体水平,以同期于我院体检的健康人群作对照,分析趋化因子受体在梅毒发生发展中的作用。结果各组受试者趋化因子受体表达水平比较二、三期梅毒患者与一期梅毒患者比较,外周血CCR3水平增高,CCR5水平降低,比较差异具有统计学意义(P0.05);二、三期梅毒患者与正常对照组比较,外周血CCR3水平增高,CCR5水平降低,比较差异具有统计学意义(P0.05);三期梅毒患者与二期梅毒患者比较,外周血CCR3水平增高,比较差异具有统计学意义(P0.05)。结论趋化因子受体在各期梅毒患者体内的免疫应答中可能起着重要作用,提示免疫调节可能是治疗梅毒的新方向。     

卡介菌多糖核酸对早期隐性梅毒患者外周血T细胞亚群的影响

目的 探讨卡介菌多糖核酸(BCG-PSN)对早期隐性梅毒患者外周血T细胞亚群表达的影响.方法 将30例早期隐性梅毒患者随机分为病例对照组与BCG-PSN组,病例对照组按常规青霉素驱梅方案治疗,BCG-PSN组除常规驱梅治疗外加用BCG-PSN;以健康志愿者15例为正常对照组.采用流式细胞术对早期隐性梅毒患者治疗前后外周血T细胞亚群表达进行检测.结果 早期隐性梅毒患者治疗前外周血中CD3+、CD4+T细胞百分率和CD4+/CD8+比值较正常对照组显著降低,差异均有极显著性意义(均P<0.01);CD8+T细胞百分率高于正常对照组,差异有显著性意义(P<0.05).治疗后,BCG-PSN组外周血CD3+、CD4+T细胞百分率及CD4+/CD8+比值均较治疗前显著升高(均P<0.01);而病例对照组治疗后外周血CD3+、CD4+T细胞百分率及CD4+/CD8+比值与治疗前比较,差异均无显著性意义(均P0.05).结论 早期隐性梅毒患者细胞免疫抑制明显,BCG-PSN可纠正早期隐性梅毒患者T细胞亚群失衡,改善其细胞免疫失调,提示BCG-PSN是一种有效的免疫调节剂,可作为梅毒的辅助治疗药物.     

SLE患者外周血淋巴细胞亚群变化的临床意义

目的 探讨淋巴细胞亚群在系统性红斑狼疮(SLE)病人发病中的临床意义.方法 采用流式细胞术检测了70例SLE患者(其中活动期38例,非活动期32例)以及30例健康体检者外周血CD3+/CD4+、CD3+/CD8+、CD3+/CD19+、NK(CD3+/CD16++CD56+)细胞的表达水平.结果 与正常对照组相比,活动期SLE患者CD4+、NK细胞百分率明显降低(P＜0.05),CD8+、B(CD19+)细胞百分率明显升高(P＜0.05),CD4+/CD8+比值显著降低(P＜0.01).SLE患者活动期与非活动期比较,CD4+细胞数低于稳定期,CD8+细胞数明显高于稳定期.结论 SLE患者外周血淋巴细胞亚群细胞数的变化与疾病的病程和临床表现相关联.     

SLE患者T细胞亚群及CD4+CD25+T细胞的检测及意义

目的探讨T淋巴细胞亚群及CD4 CD25 T细胞在SLE病人发病中的临床意义。方法采用流式细胞术检测了68例SLE患者(其中活动期病人38例,稳定期病人30例)以及30例健康体检者外周血CD3 CD4 、CD3 CD8 、CD4 CD45RA 、CD8 CD28 、CD8 CD28-T细胞亚群以及CD4 CD25 T细胞水平。结果与正常对照组相比,活动期SLE病人CD3 CD4 、CD4 CD45RA 细胞亚群的百分率明显降低(P=0.000,P=0.001),CD3 CD8 、CD8 CD28-细胞亚群的百分率明显升高(P=0.000,P=0.000)。稳定期患者CD8 CD28 细胞水平明显高于活动期和对照组(P=0.011,P=0.435),CD3 CD4 、CD4 CD45RA 水平高于活动期,但无显著性差异(P=0.067,P=0.081),CD8 CD28-T细胞亚群无明显变化(P=0.997)。活动期病人CD4 CD25 T细胞百分率明显低于正常对照组及稳定期病人(P=0.000,P=0.000),稳定期病人与对照组之间无显著性差异(P=0.572)。结论SLE患者T淋巴细胞亚群的水平是异常的。病人外周血CD8 CD28-T细胞亚群的比例升高与疾病的病程和临床表现相关联,它的升高在疾病的稳定中起重要作用。CD4 CD25 T细胞水平降低可能是导致机体抑制自身免疫反应的功能减弱并引发SLE发生发展的重要因素。     

系统性红斑狼疮(SLE)患者外周血T淋巴细胞亚群的变化及其临床意义

目的:研究系统性红斑狼疮(SLE)患者外周血T淋巴细胞亚群的变化及其临床意义。方法:采用流式细胞术对50例患者和30例健康体检者外周血中的T淋巴细胞亚群的变化进行检测。结果:与正常对照相比,活动期SLE患者CD3+CD4+细胞数明显降低(p0.05),CD3+CD8+细胞数明显升高(P0.05),CD3+CD4+/CD3+CD8+比值显著降低(P0.01)。结论:活动期SLE患者淋巴细胞亚群存在异常,其是SLE发病的重要机制之一。     

趋化因子受体CCR5及其配体在类风湿关节炎患者滑液及滑膜中的表达

目的查明趋化因子C-C亚族受体5(CCR5)及其配体在外周血、关节滑膜和滑液的表达及分布,探讨Th1细胞选择性聚集于类风湿关节炎(RA)患者关节中的机制.方法采用两色和三色免疫荧光标记、流式细胞术及激光扫描共聚焦显微技术,对15例RA患者外周血、关节液及滑膜中Th细胞亚群,以及趋化因子受体CCR5和CXCR3的表达细胞,和C-C亚族趋化因子巨噬细胞炎性蛋白(MIP)-1β的产生细胞,进行了测定和分析比较.结果(1)RA患者关节滑液细胞内细胞因子分泌模式明显向Th1偏移,Th1样细胞在关节内占优势.(2)RA患者滑液中T细胞受体CCR5的表达率为52%±8%,CXCR3的表达率为61%±12%,与自身及正常人(外周血单个核细胞)比较明显升高(P＜0.01).(3)RA患者滑膜组织中大量浸润的T细胞(尤其是CD4+细胞)、单核/巨噬细胞(Mo/Mac)、B细胞多表达CCR5的配体MIP-1β.结论RA患者的关节内,T细胞、B细胞、Mo-Mac产生MIP-1β、RANTERS等趋化因子,能趋化表达CCR5、CXCR3的Th1细胞选择性进入关节组织,导致Th1/Th2细胞失衡.     

Expression of caspase-3 and TRAIL receptors in CD4+ and CD8+ T cells of SLE patients

Objective: To study the expression of caspase-3 and tumor necrosis factor-related apoptosisinducing ligand (TRAIL) receptors in the CD4 and CD8 T cells of systemic lupus enythematosus (SLE) patients. Methods: RT-PCR was used to analyze the expression of caspase-3 and TRAIL receptors in CD4 and CD8 T cells of SLE patients and normal subjects. Results: The death domain-containing TRAIL-R1/R2 as well as “decoy“ TRAIL-R3/R4 were co-expressed in majority of CD4 and CD8 T cells in both SLE patients and normal subjects. The CD8 T cells from SLE patients showed significantly higher expression of caspase-3 and TRAIL-R2 than those from normal subjects,and the expression was correlated with the activity of the disease. Conclusion: The TRAIL-R2 signal pathway might contribute to the apoptosis of T cells in SLE.     

fas介导系统性红斑狼疮患者Foxp3+CD4+CD25+Treg细胞凋亡的研究

目的 探讨fas凋亡信号传导途径在系统性红斑狼疮(SLE)患者Foxp3+CD4+CD25+Treg凋亡异常中的作用.方法 选取活动期SLE患者25例、缓解期SLE患者20例及健康对照25名为研究对象,检测所有研究对象外周血Foxp3+CD4+CD25+Treg表面fas的表达,同时分析CD4+CD25+T细胞Foxp3表达.并分别将fas表达率及Foxp3表达率与病情活动性(SLEDAI评分)进行相关分析.结果 (1)外周血Foxp3+CD4+CD25+Treg上fas的表达:活动期SLE组为(23.72±2.35)%,缓解期SLE组为(14.0±2.1)%,对照组为(10.1±1.2)%,在活动期SLE组明显高于缓解期SLE组(P＜0.01)和对照组(P＜0.01),而缓解期SLE组与对照组差异无统计学意义(P＞0.05),fas在Foxp3+CD4+CD25+Treg上的表达与SLEDAI评分呈正相关(r=0.336,P＜0.05).(2)外周血CD4+CD25+T细胞Foxp3的表达:活动期SLE组为(2.83±0.30)%,缓解期SLE组为(5.38±0.63)%,对照组为(8.12-±0.70)%.活动期SLE组外周血 CD4+CD25+T细胞Foxp3表达明显低于缓解期SLE组(P＜0.01)和对照组(P＜0.01);而缓解期SLE组亦低于对照组(P＜0.05).外周血Foxp3表达与SLEDAI评分呈负相关(r=-0.581,P＜0.01).(3)Foxp3与fas的表达呈负相关(r=-0.349,P＜0.01).结论 SLE患者中存在由fas介导的Foxp3+CD4+CD25+Treg的过度凋亡,这可能是导致SLE病情活动的机制之一.

Abstract：

Objective To explore the role of fas apoptosis signal transduction pathway in the abnormal apoptosis of Foxp3 + CD4 + CD25 + Treg in patients with systemic lupus erythematosus ( SLE ).Methods Twenty-five active SLE patients, 20 remission SLE patients and 25 controls were selected. The level of fas expression on peripheral blood Foxp3 + CD4 + CD25 + Treg surface was detected in SLE patients.And analyzed the expression rate of Foxp3 on CD4 + CD25 + T cells was analyzed to explore the relationship between the expression rate and disease activity. Results ( 1 ) The expression rate of fas on Foxp3 + CD4 +CD25 + Treg was (23.72 ± 2. 35 )% , ( 14. 0 ± 2. 1 )% in active and remission SLE groups respectively versus ( 10. 1 ± 1.2)% in control group. The fas expression rate of active SLE group was significantly higher than those of remission SLE group( P ＜ 0. 01 ) and control group ( P ＜ 0. 01 ). And the remission SLE and control groups were not statistically significant ( P ＞0. 05 ). The expression rate of fas on the Foxp3 + CD4 +CD25 + Treg was positively correlated with the SLEDAI ( SLE disease activity index ) score ( r = 0. 336, P ＜0.05). (2) The expression rate of Foxp3 on CD4 +CD25 +T cells was (2.83 ±0.30)%, (5.38 ±0. 63 ) % in active and remission SLE groups respectively versus ( 8. 12 ± 0. 70 ) % in control group. The expression rate of Foxp3 was significantly lower in active SLE group than that in remission SLE group ( P ＜0. 01 )and control group( P ＜0. 01 ). And the Foxp3 expression rate of remission group was also lower than that of control group ( P ＜ 0.05 ). The expression rate of Foxp3 was negatively correlated with the SLEDAI score (r = -0. 581, P ＜ 0. 01 ). (3) The expression rate of Foxp3 was negatively correlated with fas (r=- 0. 349, P ＜ 0. 01 ). Conclusion The abnormal apoptosis of Foxp3 + CD4 + CD25 + Treg mediated by the fas apoptosis signal transduction pathway may be one of the pathogenic mechanisms of disease activity in SLE patients.     

系统性红斑狼疮患者外周血T细胞CTLA-4表达及其临床意义的研究#

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（PBMCs）,以抗-CD3、抗-CD28刺激培养48h,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（SLE Disease Activity Index,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细胞中、主要是CD25+T细胞中CTLA-4+细胞的比例较正常人显著增高,且与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细胞体外再活化的能力减弱有关。     

系统性红斑狼疮患者外周血CD4+CD25high Treg上PD-1分子的表达分析

目的：检测系统性红斑狼疮（systemic lupus erythematosus,SLE）患者外周血CD4＋CD25highTreg及其程序性死亡受体-1（programmed death-1,PD-1）分子的表达,探讨Treg和PD-1表达在SLE中的意义。方法：流式细胞仪检测SLE患者组、正常对照组外周血CD4＋T细胞中的CD4＋CD25highTreg和CD4＋CD25lowT细胞的比例,及其PD-1分子的表达率。结果：CD4＋CD25highTreg在SLE患者组外周血中CD4＋T细胞的比例（0.63±0.31）%与正常对照组（2.07±0.74）%相比明显降低（P〈0.05）,该亚群细胞上PD-1＋的百分率（24.99±18.65）%与对照组（6.97±1.92）%相比显著增高（P〈0.05）;CD4＋CD25lowT细胞的百分率（13.40±8.47）%及其PD-1＋的百分率（2.70±3.06）%与正常对照组（20.16±11.89）%和（0.43±0.36）%相比,差异有统计学意义（P〈0.05）。结论：外周血CD4＋CD25highTreg数量下降及其PD-1分子表达上调可能在SLE中有重要意义。     

系统性红斑狼疮患者糖皮质激素联合免疫抑制剂治疗前后外 周血NK细胞和受体表达变化及其治疗作用机制 

目的:探讨经糖皮质激素联合免疫抑制剂干扰素γ（IFN-γ）治疗前后系统性红斑狼疮（SLE）患者外周血中自然杀伤细胞（CD3－CD56+NK细胞）及其
激活性、抑制性受体表达的变化,阐明其治疗SLE的作用机制。方法：选取26例SLE患者和16例健康对照者,采用流式细胞术检测2组受试者治疗前、治疗4和12周后外周血CD3－CD56+NK细胞比率及其激活性受体和抑制性受体表达率。结果：与健康对照组比较,治疗前SLE患者CD3－CD56+NK细胞比率明显降低（P<0.05）,其激活性受体NKG2C+、NKP30+和NKP46+ 的表达率均明显增高（P<0.05）,抑制性受体KIR2DL3+、 KIR3DL1+和NKG2A+的表达率均明
显降低（P<0.05）,IFN-γ+ CD3－CD56+NK细胞比率明显增高（P<0.001）。与治疗前比较,治疗4和12周后SLE患者CD3－CD56+NK细胞比率均明显增高（P<0.05）;治疗4周后SLE患者CD3－CD56+NK细胞激活性受体NKG2C+、NKP30+和NKP46+ 的表达率均明显降低（P<0.05）,治疗12周后上述受体表达率均进一步降低（P<0.05）。治疗4周后SLE患者CD3－CD56+NK细胞抑制性受体KIR2DL3+、KIR3DL1+和NKG2A+的表达率较治疗前均明显增高（P<
0.05）,治疗12周后CD3－CD56+NK细胞 KIR3DL1+、CD158a+、CD158b+和NKG2A+的表达率较治疗前均明显增高（P<0.05）。与治疗前比较,治疗4和12周后SLE患者IFN-γ+CD3－CD56+NK　细胞比率均明显降低（P<0.001）。结论：NK细胞及其受体的变化可能与SLE的发病有关,糖皮质激素联合免疫抑制剂可能通过调节NK细胞及其受体的变化发挥治疗作用。
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Expression of chemokine receptors CCR3,CCR5 and CXCR3 on CD4+ T cells in CBA/JxDBA/2 mouse model,selectively induced by IL-4 and IL-10,regulates the embryo resorption rate

Background Chemokines and their receptors have been a research focus in transplantation immunology.Chemokines and their receptors play a role in lymphocyte recruitment and differentiation process.This study aimed to observe whether IL-4 and IL-10 may regulate the expression of chemokine receptors CCR3,CCR5 and CXCR3 on CD4+ T cells in CBA/JxDBA/2 mouse model and to explore the role of CCR3,CCR5,CXCR3 in immune tolerance in pregnancy.Methods The mouse model of spontaneous abortion (CBA/JxDBA/2) and the normal pregnant mouse model (CBA/JxBALB/c) were used.CBA/JxDBA/2 mice were injected with IL-4 (CBA/JxDBA/2-1L-4),IL-4 and IL-10 (CBA/JxDBA/2-1L-4+IL-10),or normal saline (CBA/JxDBA/2-NS) as a control.The expression of CCR3,CCR5 and CXCR3 on CD4+ T cells from mouse peripheral blood was measured by the double-labelled FCM method,and the embryo resorption rate was also examined.Results The embryo resorption rate in the CBA/JxDBA/2 group without any treatment was significantly higher than that in the CBA/JxBALB/c group (17.9% vs 3.7%,P＜0.01).The embryo resorption rate in the CBA/JxDBA/2 group immunized with IL-4 or IL-4 together with IL-10 was significantly decreased,compared with that in the control and NS groups respectively.CCR3 expression on CD4+ T cells in the CBA/JxDBA/2 group without any treatment was significantly lower than that in the CBA/JxBALB/c group (0.3738±0.3575 vs 1.2190±0.2772,P＜0.01 );both CCR5 (3.0900±1.5603 vs 1.2390±0.6361,P ＜0.01)and CXCR3 (2.4715±0.9074 vs 0.9200±0.5585,P ＜0.01 ) expressions on CD4+ T cells of the CBA/JxDBA/2 group without any treatment were significantly higher than those of the CBA/JxBALB/c group.Significant up-regulation of CCR3 and down-regulation of CXCR3 were found in the CBA/JxDBA/2 group treated with IL-4 (CCR3:2.0360±0.6944,CXCR3:1.3510±0.5263,P ＜0.01) or IL-4 and IL-10 (CCR3:1.8160±1.0947,CXCR3:1.0940±0.7168,P＜0.01).Because of the CCR5,IL-4 and IL-10 (1.9400±0.8504 vs 3.0900±1.5603,P ＜0.05),but IL-4 alone (2.5310±1.3595 vs 3.0900±1.5603,P ＞0.05)treatment significantly decreased the expression of CCR5 in CBA/JxDBA/2.Conclusions The abnormal expression of CCR3,CCR5 and CXCR3 on CD4+ T cells may play an important role in the pathogenesis of spontaneous abortion.The pregnancy immune tolerance may be induced through selective induction of CCR3,CCR5 and CXCR3 expressions by IL-4 together with IL-10.     

Relationship between expression of chemokine receptors CCR3, CCR5 and CXCR3 on CD4+ T cells and spontaneous abortion in mice

Background Previous studies have shown that local immune cells in the feto-maternal interface are recruited from peripheral blood, and that chemokines and their receptors play an initial and key role in this recruitment process. In this study, we aimed to determine whether spontaneous abortion is associated with the expression of chemokine receptors CCR3, CCR5, and CXCR3 on CD4^＋ T cells.
Methods Peripheral blood, spleen, and thymus were collected from the spontaneous abortion mouse model CBA/JxDBA/2 （SA group, n=14）, the normal pregnant mouse model CBA/JxBALB/c （NP group, n=13）, and normal non-pregnant CBA/J mice （NNP group, n=11）. The number of chemokine receptors CCR3, CCR5, and CXCR3 expressed on CD4^＋ T cells was measured by double-label flow cytometry （FCM） method.
Results In peripheral blood, the SA group had significantly lower CCR3 expression （P 〈0.01） and higher CCR5 and CXCR3 expression （P 〈0.01） on CD4^＋ T cells than did the NP group. But comparing these chemokines between the SA and NNP groups, there was no significant difference （P 〉0.05）. In spleen, the SA group expressed significantly lower CCR3 expression （P 〈0.01） and higher CCR5 and CXCR3 expression （P 〈0.05） on CD4^＋ T cells than did the NP group. When compared with the NNP group, the SA group had significantly higher CCR3 expression （P 〈0.01）, but was not statistically different with regards to the other two chemokines （P 〉0.05）. In thymus, the SA group had significantly lower CCR3 expression （P 〈0.05） and higher CXCR3 expression （P 〈0.05） on CD4^＋ T cells than the NP group, with no significant difference in CCR5 expression （P 〉0.05）. Compared with the NNP group, the SA group had higher CCR3 expression （P 〈0.01）, but there was no statistical difference in CXCR3 and CCR5 expression （P 〉0.05） between the two groups.
Conclusion The abnormal expression of CCR3, CCR5 and CXCR3 on CD4^＋ T cells may play an important role in the pathogenesis of spontaneous abortion.     

启动子区H3K27me3修饰异常促使系统性红斑狼疮患者CD4+T细胞CREMα过表达

目的 探讨SLE中CREMα表达升高的原因.方法 分离5名正常对照和5名SLE患者的CD4+T细胞,用染色质免疫沉淀(ChIP)微阵列法对各种基因启动子区组蛋白H3赖氨酸27三甲基化(H3K27me3)的水平进行分析.随后分离30名正常对照和30名SLE患者的CD4+T细胞,用ChIP结合实时定量PCR检测CREMα启动子区H3K27me3、H3K27去甲基化酶JMJD3和UTX、H3K27甲基转移酶EZH2的水平,采用实时定量RT-PCR检测CREMα mRNA水平.结果 SLE CD4+T细胞的CREMα启动子区H3K27me3水平是正常对照的0.23倍.随后通过ChIP结合实时定量PCR,我们证实了SLE患者CD4+T细胞CREMα启动子区H3K27me3水平显著降低(P<0.001),且与CREMα mRNA水平呈显著负相关(P<0.001).该区的JMJD3水平显著升高(P<0.001),且与H3K27me3水平呈负相关(P<0.001),与CREMα mRNA水平呈正相关(P<0.001).而UTX(P=0.172)及EZH2 (P=0.281)水平则与对照组无明显差异.结论 SLE CD4+T细胞CREMα启动子区JMJD3增多,导致该区H3K27me3水平降低,结果促使CREMα过表达,最终引起SLE的发病.     

系统性红斑狼疮患者外周血CD4+ CD39+ T细胞中FOXP3蛋白的表达及糖皮质激素对其影响

目的 研究系统性红斑狼疮(SLE)患者外周血CD4+ CD39+ T细胞中FOXP3蛋白的表达情况,以及糖皮质激素治疗的影响.方法 采用流式细胞术检测47例SLE患者(其中29例为初发未经治疗的活动期SLE)和22名正常人外周血CD4+ CD25+ CD39+ T细胞、CD4+CD25+ FOXP3+ T细胞及CD4+ CD39+ FOXP3+ T细胞百分率以及FOXP3蛋白的表达,分析3组细胞之间的相关性及糖皮质激素治疗的影响.结果 SLE活动组、缓解组、正常对照组外周血CD4+ CD25+ CD39+ T细胞百分率分别为(1.3±0.5)%、(1.9±0.8)%、(2.3±1.0)%,该群细胞在SLE活动组中的表达水平低于缓解组和正常对照组(均P<0.05),而在后2组之间差异无统计学意义(P>0.05);SLE活动组中CD4+ CD25+、CD4+ CD25high及CD4+ CD39+ T细胞表达的FOXP3蛋白百分率分别为(45±12)%、(65±14)%、(70±14)%,FOXP3蛋白在CD4+ CD39+ T细胞和CD4+ CD25highT细胞中的表达水平明显高于在CD4+CD25+T细胞中的表达水平(P<0.01),而在CD4+ CD39+T细胞与CD4+CD25highT细胞中的表达水平差异均无统计学意义(均P>0.05).结论 CD39可能是调节性T细胞较好的表面标记,CD39+ Treg细胞表达异常可能参与SLE的发病机制.