骨髓增生异常综合征细胞及亚群的变化

应用单克隆抗体及绵羊红细胞E玫瑰花环形成实验对22例骨髓增生异常综合征(MDS)病人的外周血T细胞总数及亚群变化进行了测定,结果表明MDS病人总T细胞减低,辅助T细胞亦减低,OKT_4/OKT_8比例失调,提示MDS发病病因中存在由T细胞数量之间平衡失调而导致的造血异常。同时,我们测定了病人的免疫球蛋白定量,结果表明MDS病人组IgG和IgA均较正常人组低,可能与T细胞亚群变化有关。本文将对22例MDS病人用表面受体和单克隆抗体来确定的T淋巴细胞亚群及所测得的免疫球蛋白的结果分析讨论。     

环孢素A治疗再障和骨髓增生异常综合征T淋巴细胞异常激活的变化

研究再生障碍性贫血(AA)用环孢素A(CsA)治疗前后和骨髓增生异常综合征(MDS)患者外周血CD4+、CD8+T淋巴细胞培养前后早期激活标志CD69的表达及其意义。将外周血在PHA20μg/ml条件下进行全血细胞培养,于0h和4h分别用双色免疫荧光标记流式细胞仪对CD4+、CD8+T淋巴细胞CD69的表达进行分析。发现PHA刺激前初治SAA和MDS-RA+MDS-RAS患者CD4+、CD8+细胞CD69的表达率增高,CAA与RAEB+RAEB-T患者CD8+细胞CD69的表达率增高;PHA刺激后AA与MDS患者CD4+、CD8+细胞表达CD69明显增强,AA患者CD4+细胞CD69的表达率高于CD8+细胞。CsA治疗后SAA患者PHA刺激前CD4+、CD8+细胞CD69的表达率较治疗前明显减低,CAA患者CD8+细胞CD69的表达率较治疗前明显减低。治疗后AA患者PHA刺激后CD4+、CD8+细胞CD69的表达率较治疗前明显减低。CsA治疗有效的AA患者治疗前PHA刺激前后CD4+、CD8+细胞CD69的表达率明显增高,治疗后明显减低。初治AA患者PHA刺激前后CD4+细胞CD69的表达率均明显高于MDS患者。说明T细胞早期活化及其活化潜能增强,以及产生针对自身造血干/祖细胞的细胞毒效应在AA和MDS发病中起重要作用,CsA能抑制AA患者T细胞的早期激活。     

重型再生障碍性贫血和骨髓增生异常综合征骨髓中T辅助细胞亚群的变化

为研究SAA和MDS骨髓Th细胞亚群的数量及比例改变情况。用FACS同期对照研究 16例正常对照组、 2 4例发病期SAA、 15例MDS骨髓Th细胞的改变。结果显示 ,正常对照组Th1、Th2细胞及Th1/Th2为 :0 33%、 0 34%、 1 0 0 ,发病期SAA为 :4 4 2 %、 0 4 0 %、 10 5 7,恢复期SAA为 :0 39%、 0 2 0 %、 0 92 % ,MDS为 :0 4 1%、 0 5 7%、 0 75。发病期SAA的Th1、Th2细胞均显著增高 (P <0 0 1、 0 0 5 ) ,Th1/Th2显著向Th1偏移 (P <0 0 1) ;恢复期SAA与正常对照基本相当 (P>0 0 5 )。与正常对照组比较 ,MDS组的Th1细胞未升高 (P >0 0 5 ) ,亦显著低于发病期SAA组 (P <0 0 1) ,虽然Th2细胞升高 ,但无统计学意义 (P >0 0 5 ) ,但Th1/Th2比值降低 (P <0 0 5 ) ,向Th2偏移。SAA的发病可能由于Th1细胞增多 ,Th2细胞代偿不足 ,Th1/Th2向Th1偏移 ;MDS骨髓Th1细胞改变不显著 ,Th2有增多的趋势 ,Th1/Th2向Th2偏移     

骨髓增生异常综合征来源的间充质干细胞对T细胞亚群的影响

目的:观察骨髓增生异常综合征(MDS)患者来源的间充质干细胞(MSC)对混合淋巴细胞反应体系中的T淋巴细胞亚群的影响.方法:将MDS来源的MSC,按照不同比例加入双向混合淋巴细胞培养体系中共同孵育,3 d后采用流式细胞术(FCM)和ELISA法检测其表面抗原以及上清液中细胞因子的变化.结果:MDS来源的MSC能明显抑制共孵育体系中的CD8 +T细胞亚群和IFN-γ的分泌,轻度抑制IL- 4的分泌,与正常来源的MSC抑制性没有统计学意义.结论:MSC在体外能明显抑制CD8 +T细胞(CTL)和Th1细胞,轻度抑制Th2细胞.     

骨髓增生异常综合征中的T细胞免疫

骨髓增生异常综合征(myelodysplastic syndromes,MDS)是一组肿瘤性疾病,以骨髓无效造血并向急性髓系白血病转化的风险为特点.流行病学显示自身免疫性疾病的患者发生MDS风险增加,为二者存在共同病因的假设提供了依据.MDS骨髓微环境中存在T细胞过度活化的现象.部分低危组MDS治疗药物具有抑制T细胞免疫机制,而高危组MDS的去甲基化药物则增强T细胞的抗肿瘤免疫反应,特别是免疫检查点抑制剂正在MDS中进行临床实验.因此,MDS中T细胞免疫失调的双重作用值得深思,充分认识T细胞免疫异常在M D S发病机制中的作用是形成新治疗方法的理论基础.     

42例骨髓增生异常综合征细胞遗传学研究

本研究对４２例骨髓增生异常综合征（ＭＤＳ）进行研究,采用骨髓细胞短期培养法,共１３例ＭＤＳ检出染色体异常核型,占３１％,ＭＤＳ－ＲＡＥＢ和ＲＡＥＢＴ（４１％）比ＭＤＳ－ＲＡ（２９％）异常核型检出率高（Ｐ＜０．０５）,检出７种类型染色体异常核型,染色体数量异常８例,以三体８多见,染色体结构异常５例,均为平衡易位。ＭＤＳ－ＲＡ异常核型均为数量异常,ＭＤＳ－ＲＡＥＢ、ＲＡＥＢＴ则以结构异常为主。观察中发现２例具有核型异常的ＭＤＳ－ＲＡＥＢ转化为ＡＮＬＬ－Ｍ２和ＡＮＬＬ－Ｍ５,表明ＭＤＳ染色体核型与ＭＤＳ亚型、转归和预后密切相关。     

38例骨髓增生异常综合征的细胞遗传学研究

３８例骨髓增生异常综合征的细胞遗传学研究侯梅，邓长安，张雅鸥骨髓增生异常综合征（ｍｙｅｌｏｄｙｓｐｌａｓｔｉｃｓｙｎｄｒｏｍｅ，ＭＤＳ）是一组与白血病密切相关的造血系统疾患。细胞遗传学资料表明，约５０％ＭＤＳ有核型异常，并认为ＭＤＳ中存在白血病克隆［...     

地西他滨对骨髓增生异常综合征患者分层治疗的疗效分析

目的:对不同危险度分级的骨髓增生异常综合征患者(myelodysplastic syndrome,MDS)分别给予不同剂量的地西他滨治疗,观察治疗前后CD3 +、CD4 +、CD8 +T淋巴细胞比例的变化。 方法:选取2015年8月至2018年8月于皖北煤电集团总医院接受治...     

霉酚酸酯联合环孢素A治疗GVHD后T细胞亚群的变化

为了解霉酚酸酯 (MMF )联合环孢素A (CsA )治疗移植物抗宿主病 (GVHD )后T淋巴细胞亚群的变化。我们采用免疫荧光标记和流式细胞仪技术 ,分析了 6例GVHD患者的T淋巴细胞亚群以及活化T细胞标志。发现在MMF治疗后患者的CD3+ CD4+ T细胞明显降低 ,CD3+ CD8+ T细胞明显增高 ,CD4/CD8比值下降 ;CD2 5 + CD4+ 和CD6 9+ CD8+ T细胞均升高。结果初步显示 ,MMF可能主要作用于CD3+ CD4+ T细胞 ,并与CsA在治疗GVHD方面有协同作用。     

骨髓增生异常综合征的临床与细胞遗传学研究

目的研究骨髓增生异常综合征（myelodysplastic syndrome，MDS）的细胞遗传学、血液学与预后的相互关系。方法采用骨髓直接法和24小时短期培养法制备染色体标本，用R显带技术，对50例MDS进行核型分析。结果50例MDS中，发现有异常核型22例，发生率44．0％（22／50）。异常类型6种：2例add（8）；4例-7；4例5q-；9例7q-；2例20q-；1例6q-。结论5q-，-7，7q-是MDS中最为常见的染色体核型异常，伴有5q-染色体核型异常的预后较好，而伴有-7，7q-核型异常的预后不良。细胞遗传学在MDS的诊断、病情发展和预后判断中有着至关重要的作用。     

类风湿性关节炎患者2H4+T淋巴细胞亚群的流式细胞仪分析

了解类风湿性关节炎患者免疫功能的异常变化，探讨其发病机制。方法，使用间接免疫荧光和直接免疫荧光方法对１１例ＲＡ患者和１２例健康人的外周血Ｔ淋巴细胞进行了研究。结果：ＲＡ患者与对照组比较ＣＤ３＾＋Ｔ细胞和ＣＤ＾＋４Ｔ细胞地明显变化，ＣＤ８＾＋Ｔ细胞明显减少，     

吉兰-巴雷综合征临床分期分型与T淋巴细胞亚群变化的相关性

目的探讨吉兰-巴雷综合征(GBS)临床分期分型与T淋巴细胞亚群变化的相关性。方法选择临床确诊的吉兰-巴雷综合征患者进行临床分期与分型,并用流式细胞仪检测其外周血T淋巴细胞亚群的相对计数。结果与正常组比较,急性期CD3 、CD8 、CD4 CD25 显著降低(P<0.01),CD4 /CD8 显著升高(P<0.05),CD4 无显著差异;恢复期CD8 、CD4 /CD8 恢复正常。急性期与恢复期比较,CD8 显著降低、CD4 /CD8 显著升高(P<0.05)。轻重症组CD3 、CD4 CD25 均显著降低(P<0.01),而重症组CD8 显著降低(P<0.01),CD4 /CD8 显著升高(P<0.05);但轻重症组间各指标均无显著性差异(P>0.05)。结论GBS患者急性期存在明显的T淋巴细胞亚群功能紊乱,且轻重症之间无明显差异。     

特发性血小板减少性紫癜患者T细胞及B细胞亚群变化的研究

目的 探讨特发性血小板减少性紫癜(idiopathic thrombocytopenic purpura,ITP)患者T、B淋巴细胞亚群的变化.方法 从大理州人民医院收集ITP患者和健康者的外周血,用Sysmex血液分析仪及流式细胞术分析T细胞及B细胞亚群.结果 与健康人群比较,ITP患者CD3+T细胞百分率无明显变化,CD4+T细胞百分率降低(42.39％±12.12％,P＜0.05),CD8+T细胞百分率升高(46.93％±11.99％,P＜0.05);CD19+B细胞百分率升高(14.11％±10.28％,P＜0.05),T2B细胞百分率(34.51％±9,70％,P＜0.05)、成熟B细胞百分率(30.91％±7.12％,P＜0.05)及记忆性B细胞百分率(23.31％±8.23％,P＜0.05)增多,差异均有统计学意义.ITP患者T1 B细胞、Kappa+B细胞、Lambda+B细胞百分率与健康人差异无统计学意义.结论 ITP患者外周血T细胞亚群和B细胞亚群分布发生了变化,这种变化在ITP发病中的作用尚需进一步研究.     

SARS患者T淋巴细胞亚群的改变及动态观察

目的　了解SARS患者T细胞亚群的改变及动态变化 ,探讨其发病机理及对预后的影响。方法　将住院 5 4例SARS患者分为治愈组 (31例 )与死亡组 (2 3例 )两组 ,用流式细胞仪进行T细胞亚群的动态观察。结果　治愈组与死亡组CD4 + 、CD8+ 均值在发病初的 15d内均显著低于正常值 ,死亡组更为显著 ,但两组比较P >0 .0 5 ,差异无显著性。发病 15d后治愈组CD4 + 、CD8+ 均值显著上升 ,而死亡组CD4 + 、CD8+ 均值持续低水平 ,两组比较P <0 .0 0 1,差异有非常显著性。治愈组早期 (≤15d)与后期 (>15d)CD4 + 、CD8+ 均值比较P <0 .0 0 1,差异有非常显著性。死亡组早期与后期CD4 + 、CD8+ 均值比较P >0 .0 5 ,差异无显著性。结论　SARS患者在发病初的 15d内细胞免疫功能是低下的。治愈组 15d后细胞免疫功能逐渐恢复正常 ,预后良好。而死亡组 15d后细胞免疫功能持续低水平 ,提示预后不良。发病的第 15天左右是疾病的转折点。CD4 + 值持续 <2 5 0 ,CD8+ 值持续 <2 0 0是预后不良的重要指标。     

T and B lymphocyte subsets in patients with unexplained recurrent spontaneous abortion: IVIG versus placebo treatment

PROBLEM: To investigate circulating lymphocyte subsets in women with recurrent spontaneous abortion (RSA) in relation to pregnancy outcome and to treatment with intravenous immunoglobulin (IVIG). METHOD OF STUDY: Forty-one women with a history of unexplained RSA were examined during first trimester of pregnancy before IVIG or placebo treatment and after pregnancy. The results were compared with five healthy, non-pregnant women and five women in the first trimester of normal pregnancy. Circulating lymphocyte subsets with focus on T-cell subpopulations were determined by flow cytometry. RESULTS: The proportions of human leukocyte antigen (HLA)-DR positive T cells (CD3+ HLA-DR+), T-killer/effector cells (CD8+ S6F1+) and B cells (CD19+) were increased, whereas the proportion of T-suppressor/inducer cells (CD4+ CD45RA+) was decreased during first trimester pregnancy of RSA women compared with pregnant normal controls. T and B lymphocyte subsets did not correlate with pregnancy outcome on either IVIG or placebo group. CONCLUSIONS: In RSA patients, the immune system seems to be activated in contrast to the suppression noted in normal pregnancy.     

帕金森病患者NK细胞亚群及T淋巴细胞亚群变化的临床意义

目的:探讨帕金森病(PD)不同年龄、不同病期、伴随症状患者外周血NK细胞亚群及T淋巴细胞亚群的变化及其临床意义。方法:应用先进的流式细胞仪(FCM)直接免疫荧光染色法检测47例PD患者外周血NK细胞亚群及T淋巴细胞亚群,并与健康人组进行对照与相关分析。结果:PD组CD3+、CD4+、CD8+、CD4+/CD8+水平较对照组均明显降低(P<0.05),而CD16+56水平则较对照组明显增高(P<0.05)。高龄、病情重及伴痴呆和抑郁的PD患者CD3+、CD4+、CD8+、CD4+/CD8+水平降低更显著(P<0.05)。结论:PD发病过程中存在T细胞免疫功能低下及NK细胞免疫平衡失调,高龄、病情重及伴痴呆和抑郁的患者NK、T细胞免疫功能异常降低更明显,此为PD病理生理基础赋予新的内涵,亦为PD的免疫干预性治疗提供新的途径。     

T and B lymphocyte subpopulations and activation/differentiation markers in patients with selective IgA deficiency

Selective deficiency of immunoglobulin A (IgAD) and common variable immunodeficiency (CVID) are genetically closely related diseases, both of unknown pathogenesis. A plethora of abnormalities in lymphocyte subpopulations and expression of activation markers were repeatedly documented in CVID patients, while almost no data are available about lymphocyte subpopulations in IgAD patients. We determined basic lymphocyte subpopulations and those subpopulations that were reported to be abnormal in CVID patients (CD25, human leucocyte antigen (HLA)-DR CD45RA, CD45RO, CD27, CD28 and CD29 on both CD4(+) and CD8(+) cells, CD57 and CD38 on CD8(+) cells, CD21, CD27, IgM, IgD on B lymphocytes) in 85 patients with IgAD, 47 patients with CVID and in 65 healthy controls. Statistical analysis was performed by the Mann-Whitney U-test; significant P-values were determined by means of Bonferoni's correction. Our results showed an increase in the relative number of CD8(+) cells and a decrease in the absolute number of CD4(+) cells compared to healthy people, but similar abnormalities in CVID patients were much more expressed. IgAD patients had significantly decreased expression of HLA-DR and increased expression of CD25 on CD4(+) lymphocytes, also CD29 expression was decreased on CD8(+) cells, while other activation/differentiation markers on T cells (including the expression of CD45RA and CD45RO antigens) were not changed. There were no statistically significant abnormalities in B lymphocyte developmental stages in IgAD patients compared to healthy controls. Our observation showed that the majority of T and B lymphocyte subpopulation abnormalities described previously in CVID are not present in IgAD patients.     

基因修饰树突状细胞诱导前列腺癌患者外周血T细胞亚群重排的研究

目的探讨以腺相关病毒（AAV）为载体,前列腺特异性抗原（PSA）基因转染树突状细胞（DC）诱导前列腺癌患者外周血T细胞亚群变化特点及临床意义。方法抽取30例前列腺癌患者外周血,采用密度梯度离心法分离外周血单个核细胞,以rAAV/PSA感染DC前体细胞,采用系列细胞因子诱导DC前体细胞成熟。第6天收集成熟DC并与T细胞按比例混合培养,诱导细胞毒性T淋巴细胞（CTL）。分别于DC与T细胞混合培养前后应用流式细胞术分析外周血T细胞亚群及调节性T细胞（CD4^＋CD25^＋FoxP3^＋Treg）的表达水平。结果 PSA基因转染DC刺激T淋巴细胞爆发增殖,与培养前比较,混合培养6d后CD8^＋、CD8^＋CD69^＋、CD8^＋CD28^＋T细胞的比例和CD8^＋/CD4^＋比值均明显增高,差异有统计学意义（P〈0.01）;而CD8＋CD28-T细胞和Treg细胞的比例均显著降低,差异有统计学意义（P〈0.01）。CD4^＋T细胞比例较前略有升高,但差异无统计学意义（P〉0.05）。结论 PSA基因转染DC能够有效地激活CD8＋抗原特异性CTL,下调免疫抑制性T细胞,提高患者的细胞免疫功能,为前列腺癌的免疫治疗提供新的有效策略。     

Long‐term follow‐up of peripheral lymphocyte subsets in a cohort of multiple sclerosis patients treated with natalizumab

Natalizumab, an anti‐alpha4 integrin monoclonal antibody inhibiting the adhesion of lymphocytes to the endothelium, is a widely accepted drug treatment for relapsing–remitting multiple sclerosis (RRMS). A peripheral increase of T and B lymphocytes has already been observed as an early treatment effect. This retrospective observational study was aimed to evaluate the peripheral lymphocyte subsets during a long‐term treatment follow‐up. We included 23 RRMS patients treated with natalizumab for at least 24–48 months who had pretreatment lymphocyte evaluation. Baseline values of lymphocyte subsets and CD4/CD8 ratio did not differ significantly from the 23 matched healthy subjects. The periodic (every 3–6 months) assessment of immune cell subsets was performed by flow cytometry on peripheral blood collected before drug injection. Therapy with natalizumab was confirmed to be effective during the observational period. For all patients, the increase in lymphocytes during natalizumab therapy compared to baseline at every assessment was significantly higher compared to that of overall white blood cells (2·1‐ and 1·3‐fold, respectively, P < 0·0001). Both T cell subsets were proportionally modified and the CD4/CD8 ratio did not change significantly, while B cells increased significantly compared to T and NK cells (3·2‐, 1·88‐ and 1·92‐fold, respectively, P < 0·0001). These changes remained constant throughout the 25–48‐month period of therapy. In conclusion, effective natalizumab treatment of RRMS patients was associated with the persistence of its biological effects through a stable increase of peripheral lymphocytes, mainly B cells, and an unchanged proportion of T cell subsets in long‐term follow‐up.