同种异基因抗原特异性调节性T细胞的体外扩增

目的建立用人B淋巴细胞体外获得大量的同种异基因抗原特异性调节性T(Treg)细胞的方法,以此检测扩增细胞的表型及其免疫无能性和免疫抑制性。方法第1轮扩增将免疫磁珠分选的人CD4+CD25+T细胞和人B淋巴细胞按1∶4体外混合培养,并加入外源白介素-2(IL-2)和抗-CD28;将第1轮扩增得到的Treg细胞用抗-CD3/CD28包被的免疫磁珠和IL-2刺激,做第2轮扩增以获得更多数量的抗原特异性Treg细胞,分为添加和或未添加免疫抑制剂雷帕霉素(RAPA)2组(n=3)。结果经过2轮的扩增后,在第2轮扩增中未添加RAPA组扩增1×103倍,纯度80%;添加RAPA组扩增0.8×103倍,纯度90%。添加RAPA组得到的Treg细胞的Foxp3、CT-LA4、CD39表达水平高于未添加RAPA组,但是HLA-DR变化不大;未添加RAPA组扩增得到的Treg细胞分泌低水平的IL-2、IL-17、IL-4和IFN-γ,而添加RAPA组得到的Treg细胞几乎不分泌上述各种细胞因子,前者表现出部分免疫反应无能性,后者表现出完全的免疫反应无能性,两者都表现出免疫抑制性功能特征。人B淋巴细胞扩增得到的抗原特异性Treg细胞能够极大地抑制同源抗原引起的免疫反应,而对多克隆刺激的免疫反应抑制能力较弱。结论用人B细胞体外扩增抗原特异性Treg细胞,再通过抗-CD3/CD28包被的免疫磁珠进一步刺激可以体外获得大量的抗原特异性的Treg细胞,加入RAPA后可有效地提高Treg细胞的纯度和免疫抑制力且呈现抗原特异性。     

CD4^＋CD25^＋调节性T细胞与自身免疫病

目的:CD4 CD25 调节性T细胞是一群具有免疫调节或免疫抑制功能的细胞。越来越多的实验证明,CD4 CD25 调节性T细胞在维持外周免疫耐受中起重要作用,这种T细胞的数量减少或功能缺失可导致自身免疫性疾病的发生。本文就CD4 CD25 调节性T细胞及其在自身免疫性疾病中作用的研究进展做一综述。资料来源:应用计算机检索CNKI、Medline、EMCC数据库和手工检索2006-2007年的相关文献。检索词为"CD4 CD25 T调节性细胞,自身免疫病,免疫耐受,CD4 CD25 regulatory T cell,Treg,autoimmune disease,immune tolerance"。资料选择:检索范围包括临床研究(不限研究对象的年龄、性别、种族)和基础研究,不限体内和体外研究。资料提炼:共收集到相关文献675篇,选择其中33篇英文文献进行重点阅读和分析。资料综合:CD4 CD25 调节性T细胞具有免疫抑制功能,在机体的免疫调节中发挥重要作用。与其免疫调节功能相关的杀伤性T细胞淋巴细胞相关抗原4、CD45RO、糖皮质激素诱导的肿瘤坏死因子受体、淋巴细胞的无能相关基因等细胞表面分子和白细胞介素2、白细胞介素10、白细胞介素4、转化生长因子β等细胞因子的研究不断深入。此外,CD4 CD25 调节性T细胞功能的发挥还与FOXP3的表达密切相关。CD4 CD25 调节性T细胞数量的减少、抑制功能的受损和(或)细胞表面分子表达的缺陷可能导致1型糖尿病、多发性硬化和炎症性肠病等多种自身免疫病的发生。结论:CD4 CD25 调节性T细胞主要通过细胞接触依赖机制和抑制性细胞因子依赖机制发挥免疫抑制效应。其数量的减少、功能的受损和(或)表面分子表达的缺陷与自身免疫病的发生发展密切相关。     

Marked elevation of human circulating CD4+CD25+ regulatory T cells in sepsis-induced immunoparalysis

OBJECTIVE: Immunoparalysis has recently emerged as a possible cause explaining the failure of clinical trials in septic shock. Because human peripheral blood CD4+CD25+ T cells have been characterized as suppressor T cells, we hypothesized they might be increased in sepsis-induced immunoparalysis. DESIGN: Prospective, observational, clinical study. SETTING: Adult intensive care units in a university hospital. SUBJECTS: Patients with septic shock (n = 16) and healthy individuals (n = 36). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In patients with septic shock (mortality rate at 28 days, 56%; mean admission Simplified Acute Physiology Score II, 47), we first illustrated immunoparalysis by showing a severe diminished monocytic human leukocyte antigen (HLA)-DR expression. Afterward, compared with control values, we found in these patients a marked elevation of circulating CD4+CD25+ T cells that were also CD45RO+ and CD69- and overexpressed CTLA-4. Importantly, nonsurvivors (n = 9) presented prolonged lower monocytic HLA-DR expression and higher percentage of CD4+CD25+ T-suppressor T cells. CONCLUSIONS: These data support the concept that the persistence of a pronounced immunoparalysis after septic shock is associated with a poor outcome. Whether CD4+CD25+ T cells directly participate in sepsis-induced immunoparalysis remains to be investigated.     

Antigen-dependent proliferation of CD4+ CD25+ regulatory T cells in vivo

The failure of CD25+ regulatory T cells (Tregs) to proliferate after T cell receptor (TCR) stimulation in vitro has lead to their classification as naturally anergic. Here we use Tregs expressing a transgenic TCR to show that despite anergy in vitro, Tregs proliferate in response to immunization in vivo. Tregs also proliferate and accumulate locally in response to transgenically expressed tissue antigen whereas their CD25- counterparts are depleted at such sites. Collectively, these data suggest that the anergic state that characterizes CD25+ Tregs in vitro may not accurately reflect their responsiveness in vivo. These observations support a model in which Treg population dynamics are shaped by the local antigenic environment.     

脓毒症患儿CD4+CD25+调节性T细胞的变化

目的 观察不同免疫状态下脓毒症婴幼儿外周血CD4+CD25+Foxp3high调节性T细胞(Treg细胞)及相关分子的变化,探讨婴幼儿脓毒症免疫功能紊乱的可能机制.方法 分别收集2007年5月至2007年11月深圳市儿童医院重症监护室收治的婴幼儿脓毒症36例血液标本,另选16例健康同龄儿童作为正常对照进行前瞻性研究;排除既往患有自身免疫性疾病、免疫缺陷病、遗传代谢病及肿瘤的患儿,排除近6个月曾使用影响免疫功能的药物.本研究获得深圳市儿童医院伦理委员会的同意.以外周血CD14+单核细胞HLA-DR表达>30%或<30%为阈值,将患儿分为免疫激活组(DR-H组)和免疫抑制组(DR-L组),用流式细胞术检测CD14+单核细胞HLA-DR表达率,CD4+CD25+Foxp3highTreg细胞比例;实时荧光定量PCR(Real time-PCR)检测CD4+T细胞Foxp3、CTLA-4、GITR、IL-10mRNA表达.统计方法采用单因素方差分析,P<0.05为差异具有统计学意义.结果 急性期DR-L组CD4+CD25+Foxp3highTreg细胞比例明显高于对照组及DR-H组(P<0.05).DR-L组Foxp3、CTLA-4、IL-10等相关分子基因表达高于对照组及DR-H组(P<0.05),DR-L组GITR基因表达高于DR-H组.结论 CD4+CD25+Foxp3highTreg细胞数量异常增加可能与婴幼儿脓毒症免疫抑制状态有关.     

Direct expansion of functional CD25+ CD4+ regulatory T cells by antigen-processing dendritic cells

An important pathway for immune tolerance is provided by thymic-derived CD25+ CD4+ T cells that suppress other CD25- autoimmune disease-inducing T cells. The antigen-presenting cell (APC) requirements for the control of CD25+ CD4+ suppressor T cells remain to be identified, hampering their study in experimental and clinical situations. CD25+ CD4+ T cells are classically anergic, unable to proliferate in response to mitogenic antibodies to the T cell receptor complex. We now find that CD25+ CD4+ T cells can proliferate in the absence of added cytokines in culture and in vivo when stimulated by antigen-loaded dendritic cells (DCs), especially mature DCs. With high doses of DCs in culture, CD25+ CD4+ and CD25- CD4+ populations initially proliferate to a comparable extent. With current methods, one third of the antigen-reactive T cell receptor transgenic T cells enter into cycle for an average of three divisions in 3 d. The expansion of CD25+ CD4+ T cells stops by day 5, in the absence or presence of exogenous interleukin (IL)-2, whereas CD25- CD4+ T cells continue to grow. CD25+ CD4+ T cell growth requires DC-T cell contact and is partially dependent upon the production of small amounts of IL-2 by the T cells and B7 costimulation by the DCs. After antigen-specific expansion, the CD25+ CD4+ T cells retain their known surface features and actively suppress CD25- CD4+ T cell proliferation to splenic APCs. DCs also can expand CD25+ CD4+ T cells in the absence of specific antigen but in the presence of exogenous IL-2. In vivo, both steady state and mature antigen-processing DCs induce proliferation of adoptively transferred CD25+ CD4+ T cells. The capacity to expand CD25+ CD4+ T cells provides DCs with an additional mechanism to regulate autoimmunity and other immune responses.     

Continuous activation of autoreactive CD4+ CD25+ regulatory T cells in the steady state

Despite a growing interest in CD4+ CD25+ regulatory T cells (Treg) that play a major role in self-tolerance and immunoregulation, fundamental parameters of the biology and homeostasis of these cells are poorly known. Here, we show that this population is composed of two Treg subsets that have distinct phenotypes and homeostasis in normal unmanipulated mice. In the steady state, some Treg remain quiescent and have a long lifespan, in the order of months, whereas the other Treg are dividing extensively and express multiple activation markers. After adoptive transfer, tissue-specific Treg rapidly divide and expand preferentially in lymph nodes draining their target self-antigens. These results reveal the existence of a cycling Treg subset composed of autoreactive Treg that are continuously activated by tissue self-antigens.     

睾丸内胰岛移植对CD4~+ CD25~+调节性T细胞分布的影响

背景:CD4 CD25 调节性T细胞是维持机体免疫耐受的重要调控者,参与了多种移植免疫耐受的诱导。目的:拟观察小鼠睾丸内胰岛移植后CD4 CD25 调节性T细胞分布的特点。设计、时间及地点:观察对照动物实验,2007-04/2008-01在江西省实验动物中心完成。材料:成年Balb/c小鼠。方法:分离小鼠胰岛细胞,采用胰管内注射胶原酶水浴消化及Ficoll400不连续密度梯度离心法纯化,以双硫腙染色,计算胰岛细胞纯度,以体外葡萄糖刺激胰岛素分泌试验判定胰岛细胞功能。将胰岛移植至小鼠睾丸或肾包膜下,每只移植300～400个胰岛。在胰岛移植24h后麻醉处死小鼠,取脾脏、睾丸及淋巴结,制成细胞悬液,免疫磁珠法分离CD4 CD25 T细胞,通过流式细胞仪分析计数。主要观察指标:胰岛细胞的纯度及功能,CD4 CD25 调节性T细胞的分布。结果:纯化后每只胰腺获得(478±53)个胰岛细胞,纯度为(81.5±12.3)%,纯化后细胞形态完好,活度大于90%。睾丸内胰岛移植时,睾丸、淋巴结及脾脏中CD4 CD25 调节性T细胞均显著增多(P<0.05～0.01)。结论:睾丸内胰岛移植能明显上调睾丸、淋巴结及脾脏中CD4 CD25 调节性T细胞数量。     

CD4+CD25+调节性T细胞在脓毒症预后评价中的应用

目的 探讨脓毒症患者外周血中CD4+ CD25+调节性T细胞(Treg)对脓毒症患者预后预测的价值.方法 收集上海长征医院2013年12月至2014年4月入院的28例确诊脓毒症患者,根据出院结局分为存活组和死亡组,分别于入院的第1天及第7天采集外周血,流式细胞术检测CD4+ CD25+ Treg细胞比例,以及检测血常规、CRP、胆红素、PCT、凝血功能等,并统计APACHEⅡ、SOFA评分,分析各指标第1天及第7天值以及差值对脓毒症预后的预测准确性.结果 入组28例病例,年龄(60.36 ± 15.03)岁,APACHEⅡ评分(16.68 ±7.00),SOFA评分(7.18±3.78);伴有严重创伤患者12例(42.9％),感染性休克患者10例(35.7％),死亡9例(32.2％).存活组与死亡组第1天、第7天CD4+ CD25+ Treg细胞比例中位数(四分位数)分别为:2.10％ (0.80,3.10)％vs.1.80％ (1.15,3.65)％ (Z=-0.148,P=0.883); 0.90％(0.30,2.80)％vs.5.70％ (2.60,8.30)％(Z=-2.905,P=0.004).结论 动态监测CD4+CD25+ Treg细胞能够准确预测脓毒症患者预后,具有较好的临床应用前景.     

CD4~+CD25~+调节性T细胞的一般特性及其在银屑病发病中的作用

CD4+CD25+调节性T细胞是一组具有免疫调节作用的T细胞群,对于维持机体免疫耐受和免疫应答稳态具有非常重要的作用。越来越多的研究表明,银屑病是多基因遗传背景下T细胞介导的免疫性疾病,CD4+CD25+调节性T细胞的免疫反应及其分泌的细胞因子在银屑病的发病中有着重要作用。本文主要就CD4+CD25+调节性T细胞的一般特性及其在银屑病发病机制中作用的研究进展作一综述,帮助我们更深入地了解银屑病的发病机制并为今后临床诊断和治疗提供依据。     

CCR7 is required for the in vivo function of CD4+ CD25+ regulatory T cells

CCR7-mediated migration of naive T cells into the secondary lymphoid organs is a prerequisite for their encounter with mature dendritic cells, the productive presentation of cognate antigen, and consequent T cell proliferation and effector differentiation. Therefore, CCR7 was suggested to play an important role in the initiation of adaptive immune responses. In this study, we show that primary immunity can also develop in the absence of CCR7. Moreover, CCR7-deficient knockout (KO) mice display augmented immune responses. Our data cumulatively suggest that enhanced immunity in CCR7 KO mice is caused by the defective lymph node (LN) positioning of FoxP3(+) CD4(+) CD25(+) regulatory T cells (T reg cells) and the consequent impediment of their function. The FoxP3(+) T reg cells express CCR7 and, after their adoptive transfer, migrate into the LNs of wild-type mice. Here, they proliferate in situ upon antigen stimulation and inhibit the generation of antigen-specific T cells. Conversely, transferred CCR7-deficient T reg cells fail to migrate into the LNs and suppress antigen-induced T cell responses. The transfer of combinations of naive and T reg cells from wild-type and CCR7 KO mice into syngeneic severe combined immunodeficient mice directly demonstrates that CCR7-deficient T reg cells are less effective than their wild-type counterparts in preventing the development of inflammatory bowel disease.     

不同树突状细胞对CD4~+CD25~+Foxp3~+调节性T细胞体外扩增的影响

目的利用不同种类树突状细胞(dendritic cells,DC)体外扩增获得表型和功能稳定的CD4+CD25+Foxp3+调节性T细胞(Treg)。方法免疫磁珠法(MACS)分离Balb/c小鼠CD4+CD25+调节性T细胞,利用与调节性T细胞同基因或异基因成熟DC、未成熟DC和调节性DC刺激其扩增,流式细胞术测定其纯度和表型。以CD4+CD25-T细胞作为反应细胞,验证扩增前后Treg细胞的免疫抑制功能。结果MACS分离的CD4+CD25+调节性T细胞纯度达到(95.38±1.82)%,同基因和异基因DC都能有效刺激Treg细胞体外扩增,其中同基因成熟DC扩增效果最为明显。而且同基因成熟DC扩增后CD4+CD25+调节性T细胞纯度达到(94.16±1.88)%,而且高表达Foxp3分子。当CD4+CD25+调节性T细胞与效应T细胞比例为1∶1时,能够有效的抑制效应T细胞的增殖,而且,同基因成熟DC扩增的CD4+CD25+调节性T细胞的抑制效果比新分离的Treg效果更好。结论同基因成熟DC能够体外扩增表型和功能稳定的Treg细胞。     

Defective suppressor function of human CD4+ CD25+ regulatory T cells in autoimmune polyglandular syndrome type II

In autoimmune polyglandular syndromes (APS), several organ-specific autoimmune diseases are clustered. Although APS type I is caused by loss of central tolerance, the etiology of APS type II (APS-II) is currently unknown. However, in several murine models, depletion of CD4(+) CD25(+) regulatory T cells (T(regs)) causes a syndrome resembling human APS-II with multiple endocrinopathies. Therefore, we hypothesized that loss of active suppression in the periphery could be a hallmark of this syndrome. T(regs) from peripheral blood of APS-II, control patients with single autoimmune endocrinopathies, and normal healthy donors showed no differences in quantity (except for patients with isolated autoimmune diseases), in functionally important surface markers, or in apoptosis induced by growth factor withdrawal. Strikingly, APS-II T(regs) were defective in their suppressive capacity. The defect was persistent and not due to responder cell resistance. These data provide novel insights into the pathogenesis of APS-II and possibly human autoimmunity in general.     

类风湿性关节炎患者外周血CD4^＋CD25^＋调节性T细胞的表达及意义

CD4 CD25 调节性T细胞是一种除主要表达CD25分子外,还表达CTLA-4和G ITR(糖皮质激素诱导的TNF受体)等的CD4 T细胞亚群,它不但是参与对自身抗原外周耐受的主要T细胞群,而且还作为对外来抗原应答的调节性T细胞,对于维持外周免疫耐受有重要意义[1,2]。已有研究表明,自身免疫病的易     

镓铝砷激光局部治疗对类风湿关节炎患者调节T细胞和局部炎性介质的影响

目的 探讨镓铝砷激光联合药物治疗类风湿关节炎(RA)的机制.方法 将22例RA患者分为观察组和对照组,每组11例.观察组采用镓铝砷激光+甲氨蝶呤治疗,对照组仅采用甲氨蝶呤治疗.采用流式细胞双抗染色法分别测定患者治疗前、后外周血和膝关节滑液中CD4+CD25+treg(调节性T细胞)的数量,采用酶联免疫吸附法测定治疗前、后患者膝关节滑液中前列腺素E2(PGE2)的含量.同时检测10名健康人(正常对照组)外周血CD4+CD25+treg细胞数量.结果 观察组膝关节局部症状改善优于对照组;2组治疗后膝关节滑液中PGE2含量分别为(3.82±1.34)和(1.69±0.98),均较治疗前下降,其中观察组下降幅度明显高于对照组,差异具有统计学意义(P＜0.05);患者外周血CD4+CD25+treg细胞数量为(3.84±3.20)%,明显低于正常对照组,差异存在统计学意义(P＜0.05).滑液中CD4+CD25+treg远多于外周血.观察组治疗后关节滑液中CD4+CD25+treg的数量为(9.78±10.28)%,与治疗前比较差异存在统计学意义(P＜0.05).结论 镓铝砷激光联合甲氨蝶呤治疗类风湿关节炎临床疗效优于单纯应用甲氨蝶呤,联合治疗的机制可能在于明显减少靶器官局部炎性介质和CD4+CD25+treg细胞数量.

Abstract：

Objective To explore the mechanism of combined treatment with methotrexate (MTX) and Ga-Al-As laser irradiation for rheumatoid arthritis (RA) and to assess the effectiveness of Ga-Al-As laser therapy for RA. Methods Twenty-two patients with RA were randomly and evenly divided into two groups: the treatment group treated with Ga-Al-As laser irradiation combined with MTX and the control group treated with MTX only. Ten age-matched normal subjects were observed as normal controls. The amount of CD4 + CD25 + regulatory T cells in peripheral blood (PB) of the normal controls and that in the PB and synovial fluid (SF) of the 22 patients before and after therapy were counted by flow cytometry. Meanwhile, the amount of prostaglandin E2 (PGE2) in synovial fluid of the patients was measured before and after treatment by enzyme-linked immunosorbent assay(ELISA). Results After combined treatment the clinical symptoms of the patients were improved significantly, and the amount of PGE2in SF decreased significantly. The count of CD4 + CD25 + regulatory T cells in PB of RA patients was ( 3.84 ±3.20) % , compared to ( 10.05 ± 7.04) % in healthy individuals. The count of CD4 + CD25 + regulatory T cells in SF of RA patients was ( 14.89 ± 12.30) % , much higher than that in PB. The count of CD4 + CD25 + regulatory T cells in SF decreased significantly in treatment group compared to control group (P ＜0.05). Conclusion Ga-Al-As laser irradiation eombined with MTX can effectively improve the clinical symptoms of RA patients. It may be related to the decrease of amount of PGE2 and count of CD4 + CD25 + regulatory T cell in PB and SF.     

调节性T细胞CD4~+CD25~+CD127~(low)在抗多耐药肺结核治疗中的意义

目的探讨调节性T细胞CD4+CD25+CD127low在西药联合中药复方"益肺通络方"抗多耐药结核患者中的免疫调节作用。方法选取多耐药结核病(MDR-TB)住院患者34例,随机分成标准化疗(西药)组12例作为对照组,中药复方联合西药组22例作为试验组,并签署知情同意书,按临床试验方案抗结核治疗,第0、3、6、9个月时分别采集2mL肝素抗凝外周静脉血,经CD4、CD25、CD127流式抗体标记后,Beckman流式细胞仪(FCM)计数各组CD4+CD25+CD127low百分比。结果随服药时间推移,对照组MDR-TB患者CD4+CD25+CD127low调节性T细胞百分比下降,差异无统计学意义(P0.05);试验组MDR-TB患者CD4+CD25+CD127low调节性T细胞百分比下降明显,差异有统计学意义(P=0.007);与对照组MDR-TB患者比较,试验组MDR-TB患者CD4+CD25+CD127low调节性T细胞百分比下降,差异有统计学意义(P=0.047)。结论经过9个月的抗结核治疗,试验组能有效降低MDR-TB患者CD4+CD25+CD127low调节性T细胞百分比,中药复方可能协同西药下调调节性T细胞的免疫抑制,恢复结核病患者机体免疫平衡状态。因此,中药复方联合西药抗多耐药结核患者治疗也许是一个有益的帮助。     

Highly efficient expansion of human CD4+CD25+ regulatory T cells for cellular immunotherapy in patients with graft-versus-host disease

CD4+CD25+ regulatory T cells (T(REG)) are engaged in the regulation of murine and human immune responses as well as graft-versus-host disease (GvHD) after allogeneic stem-cell transplantation. Despite their suppression of GvHD they do not impair graft-versus-tumor activity in the mouse, which makes T(REG) especially attractive candidates for cellular immunotherapy. T(REG) comprise only 5% to 10% of CD4+ T cells in peripheral blood and are naturally anergic, which prevented their use as therapeutic suppressor cells in the context of autoimmune or alloimmune reactions so far. We therefore developed an in vitro expansion protocol for human T(REG), breaking their anergy with anti-CD3/anti-CD28-coupled paramagnetic beads and a combination of interleukin (IL)-2 and IL-15. Highly purified human T(REG) can be expanded 285-fold to 1000-fold within 20 days and keep their phenotype as well as all their suppressor functions even in the context of stimulation with mature allogeneic dendritic cells. However, we demonstrate that FoxP3 is not a reliable marker for human T(REG) as it is transiently inducible in CD4+CD25- cells upon activation with cytokines or via their T cell receptor. In addition, we successfully expanded CD4+CD25+ cells from patients after allogeneic stem-cell transplantation with or without GvHD and show that different suppressor functions might be lost independently, demonstrating that human T(REG) biology is likely more complicated than previously thought.     

急性淋巴细胞白血病的免疫分型及CD4+CD25+T调节细胞检测

背景:在急性淋巴细胞白血病发病过程中,CD4+CD25+T调节细胞对机体免疫反应可能起着一定的调节作用.目的:观察急性淋巴细胞白血病患者的免疫分型及外周血CD4+CD25+T调节细胞的变化情况.方法:采用流式细胞仪对35例急性淋巴细胞白血病患者进行免疫分型,并检测外周血CD4+CD25+T调节细胞的数目,与18名健康对照作比较.结果与结论:急性B细胞淋巴细胞白血病22例,急性T细胞淋巴细胞白血病13例;22例急性B细胞淋巴细胞白血病中CD19的阳性表达率最高(100%),而13例急性T细胞淋巴细胞白血病中CD7阳性表达率最高(100%).急性B细胞淋巴细胞白血病患者外周血CD4+CD25+T调节细胞和急性T细胞淋巴细胞白血病患者差异无显著性意义(P > 0.05),但均高于健康对照(P < 0.05).表明急性B细胞淋巴细胞白血病中CD19阳性表达率最高,急性T细胞淋巴细胞白血病中CD7阳性表达率最高,同时急性淋巴细胞白血病患者外周血CD4+CD25+T调节细胞水平显著增高.