CD8 and CD4 T Cells in West Nile Virus Immunity and Pathogenesis

CD4 and CD8 T lymphocytes are adaptive immune cells that play a key role in the immune response to pathogens. They have been extensively studied in a variety of model systems and the mechanisms by which they function are well described. However, the responses by these cell types vary widely from pathogen to pathogen. In this review, we will discuss the role of CD8 and CD4 T cells in the immune response to West Nile virus infection.     

Differentially enhanced cytokine gene expression in CD4+ and CD8+ T cells in mesenteric lymph nodes in rats infected with Nippostrongylus brasiliensis

Autoinfective strongyloidiasis is potentially fatal, yet the majority of infected individuals harbour asymptomatic and chronic infections. The role of humoral responses in modulating autoinfection was assessed by examining antibody isotype responses to filariform larval antigens amongst chronically infected ex-Far East Prisoners of War (exFEPOWs) with longstanding (> 30 years) infection. Serum immunoglobulin (Ig)G1, IgG4, IgE and IgA responses to whole Strongyloides stercoralis L3 extracts and their constituent antigenic components were characterized by ELISA and quantitative immunoblotting. Comparison of two groups of S. stercoralis infected exFEPOWs with and without detectable larvae in stool demonstrated novel trends. Significantly enhanced recognition of six immunodominant antigenic components by IgA was associated with undetectable larval output, as was enhanced IgE recognition of several components. Additionally, IgE and IgG4 exhibited parallel antigen recognition patterns. These findings are consistent with roles for IgA in modulating larval output, for IgE in regulating autoinfection, and for IgG4 in blocking IgE-mediated responses in human strongyloidiasis.     

Priming of CD4+ T cells and development of CD4+ T cell memory; lessons for malaria

CD4 T cells play a central role in the immune response to malaria. They are required to help B cells produce the antibody that is essential for parasite clearance. They also produce cytokines that amplify the phagocytic and parasitocidal response of the innate immune system, as well as dampening this response later on to limit immunopathology. Therefore, understanding the mechanisms by which T helper cells are activated and the requirements for development of specific, and effective, T cell memory and immunity is essential in the quest for a malaria vaccine. In this paper on the CD4 session of the Immunology of Malaria Infections meeting, we summarize discussions of CD4 cell priming and memory in malaria and in vaccination and outline critical future lines of investigation. B. Stockinger and M.K. Jenkins proposed cutting edge experimental systems to study basic T cell biology in malaria. Critical parameters in T cell activation include the cell types involved, the route of infection and the timing and location and cell types involved in antigen presentation. A new generation of vaccines that induce CD4 T cell activation and memory are being developed with new adjuvants. Studies of T cell memory focus on differentiation and factors involved in maintenance of antigen specific T cells and control of the size of that population. To improve detection of T cell memory in the field, efforts will have to be made to distinguish antigen-specific responses from cytokine driven responses.     

The immunosuppressive effects of CD4+CD25+ regulatory T cells on dendritic cells in patients with chronic hepatitis B

The characteristics and functions of CD4⁺CD25⁺ regulatory T cells (Tregs) have been well defined in murine and human systems. However, the interaction or crosstalk between CD4⁺CD25⁺ Tregs and dendritic cells (DCs) remains controversial. In this study, the effects of chronic hepatitis B (CHB) CD4⁺CD25⁺ Tregs on the maturation and function of monocyte‐derived DCs were examined. The results showed that CD4⁺CD25⁺ render the DCs inefficient as antigen‐presenting cells (APCs) despite prestimulation with CD40 ligand. This effect was marginally reverted by applying neutralizing antibodies (Abs) to IL‐10 and TGF‐β. There were an increased IL‐10 and TGF‐β secretion and reduced expression of costimulatory molecules in DC. Thus, in addition to a direct suppressor effect on CD4⁺T cells, CD4⁺CD25⁺ may modulate the immune response through DCs in CHB patients.     

支气管哮喘大鼠CD4^＋CD25^＋T细胞的变化及地塞米松干预作用的研究

目的研究支气管哮喘（简称哮喘）大鼠模型支气管肺泡灌洗液（BALF）、血液、脾脏CD4^＋CD25^＋T细胞的变化,及地塞米松对CD4^＋CD25^＋T细胞的影响。方法50只SD大鼠随机分为5组,空白对照（A）组,哮喘（B）组,地塞米松1（C）组、地塞米松2（D）组,地塞米松3（E）组。A组第1天给予腹腔注射生理盐水1ml,第15～21天每天给予生理盐水雾化。B、C、D、E组用卵蛋白建立哮喘大鼠模型,第1天,每只大鼠腹腔注射抗原1ml（卵蛋白1mg＋灭活百日咳杆菌9×10。个＋氢氧化铝干粉100mg）混悬液,第15～21天给予1％的卵蛋白雾化30min,C、D、E组于雾化后分别给予腹腔注射地塞米松0．2mg／kg、1mg／kg、2mg／kg。采用流式细胞仪检测的方法,观察大鼠体内BALF、外周血、脾脏CD4^＋CD25^＋T细胞的变化及使用不同剂量地塞米松后对其的影响。结果B组BALF、外周血、脾脏CD4^＋CD25^＋T细胞表达占CD4^＋T细胞的百分比分别是（42．21±5．62）％、（12．69±2．70）％、（11．15±1．05）％,A组结果分别是（18．76±5．85）％、（6．21±1．73）％、（7．85±2．13）％。B组与A组比较,差异均具有统计学意义（P〈0．01,P〈0．01,P〈0．05）;C组、D组、E组BALF中CD4^＋CD25^＋T细胞占CD4^＋T细胞的百分比表达分别是（10．49±4．03）oA、（13．28±5．12）％、（7．51±5．39）％,显著低于A组和B组,（P〈0．05,P〈0．01）;外周血中,C组（6．03±1．43）％、D组（4．88±0．95）％与A组（6．21±1．73）％比较,差异无统计学意义,E组（3．49士0．62）％与C组、A组比较,差异有统计学意义（P〈0．05）。脾脏中,c组（7．25±1．82）%、D组（8．63±3．18）％与A组（7．85±2．13）％比较,差异无统计学意义,E组（3．38±1．37）％与C组、D组、A组比较,差异有统计学意义（P〈0．05）。结论CD4^＋CD25^＋T细胞在哮喘大鼠体内有明显的优势表达,可能是哮喘发病的机制之一。地塞米松可以抑制CD4^＋CD25^＋T细胞的表达。BALF内CD4^＋CD25^＋T细胞的变化与外周血和脾脏的变化具有一致性,监测外周血或脾脏CD4^＋CD25^＋T细胞变化可了解肺部情况。     

支气管哮喘大鼠CD4+CD25+T细胞的变化及地塞米松干预作用的研究

目的 研究支气管哮喘(简称哮喘)大鼠模型支气管肺泡灌洗液(BALF)、血液、脾脏CD4+CD25+T细胞的变化,及地塞米松对CD4+CD25+T细胞的影响.方法 50只SD大鼠随机分为5组,空白对照(A)组,哮喘(B)组,地塞米松1(C)组、地塞米松2(D)组,地塞米松3(E)组.A组第l天给予腹腔注射生理盐水l ml,第15～21天每天给予生理盐水雾化.B、C、D、E组用卵蛋白建立哮喘大鼠模型,第1天,每只大鼠腹腔注射抗原l ml(卵蛋白1 mg+灭活百日咳杆菌9×106个+氢氧化铝干粉100 mg)混悬液,第15～21天给予1%的卵蛋白雾化30 min,C、D、E组于雾化后分别给予腹腔注射地塞米松0.2 mg/kg、1 mg/kg、2 mg/kg.采用流式细胞仪检测的方法 ,观察大鼠体内BALF、外周血、脾脏CD4+CD25+T细胞的变化及使用不同剂量地塞米松后对其的影响.结果 B组BALF、外周血、脾脏CD4+CD25+T细胞表达占CD4+T细胞的百分比分别是(42.21±5.62)%、(12.69±2.70)%、(11.15±1.05)%,A组结果 分别是(18.76±5.85)%、(6.21±1.73)%、(7.85±2.13)%.B组与A组比较,差异均具有统计学意义(P＜0.01,P＜0.01,P＜0.05);C组、D组、E组BALF中CD4+CD25+T细胞占CD4+T细胞的百分比表达分别是(10.49±4.03)%、(13.28±5.12)%、(7.51±5.39)%,显著低于A组和B组,(P＜0.05,P＜0.01);外周血中,C组(6.03±1.43)%、D组(4.88±0.95)%与A组(6.21±1.73)%比较,差异无统计学意义,E组(3.49±0.62)%与C组、A组比较,差异有统计学意义(P＜0.05).脾脏中,C组(7.25±1.82)%、D组(8.63±3.18)%与A组(7.85±2.13)%比较,差异无统计学意义,E组(3.38±1.37)%与C组、D组、A组比较,差异有统计学意义(P＜0.05).结论 CD4+CD25+T细胞在哮喘大鼠体内有明显的优势表达,可能是哮喘发病的机制之一.地塞米松可以抑制CD4+CD25+T细胞的表达.BALF内CD4+CD25+T细胞的变化与外周血和脾脏的变化具有一致性,监测外周血或脾脏CD4+CD25+T细胞变化可了解肺部情况.     

不同程度的非酒精性脂肪肝患者CD4+ CD25+ Foxp3T细胞的检测及其意义

目的 探讨不同程度的非酒精性脂肪肝患者的CD 4+ CD 25+ Foxp 3T细胞水平的变化.方法 应用流式细胞术检测不同程度的非酒精性脂肪肝60例患者和20例健康体检者外周血的CD 4+ CD 25+和CD 4+ CD 25+ Foxp 3的比例.结果 非酒精性脂肪肝组外周血CD 4+ CD 25+细胞占CD 4+...     

扩张型心肌病患者CD4~+CD25~+Foxp3~+ T细胞的检测及意义

目的:探讨扩张型心肌病(DCM)患者外周血CD4+CD25+Foxp3+T细胞的水平及意义。方法:采用流式细胞术检测DCM患者30例及健康对照组20例外周血CD4+CD25+T细胞和CD4+CD25+Foxp3+T细胞的比例。结果:DCM患者外周血CD4+CD25+T细胞占CD4+T细胞的比例为(8.53±1.64)%,显著低于健康对照组的(11.4±2.17)%,P0.01;DCM患者CD4+CD25+Foxp3+T细胞占CD4+T细胞比例为(0.99±0.54)%,显著低于健康对照组的(1.55±0.55)%,P0.01;且DCM患者心功能越差,CD4+CD25+Foxp3+T细胞占CD4+T细胞的比例越低。结论:DCM患者调节性T细胞比例的减少,可能打破了自身免疫耐受,发生了针对心肌抗原的自身免疫反应,参与了DCM的发病。     

不稳定心绞痛患者CD4+CD25+调节性T细胞检测及意义

目的探讨不稳定性心绞痛患者外周血CD4 CD25 调节性T细胞(Treg)水平及意义。方法采用流式细胞分析法,检测13例不稳定性心绞痛患者、8例稳定性心绞痛患者和10例胸痛综合征患者外周血CD4 CD25 Treg占CD4 T细胞比例。结果不稳定性心绞痛患者外周血 Treg/CD4 T细胞比例(10．1±3．4％)显著低于稳定性心绞痛组(14．2±2．9％)和胸痛综合征组 (16．5±4．9％)。结论不稳定性心绞痛患者外周血Treg比例减少。Treg比例降低可能打破了外周免疫耐受,参与了动脉粥样硬化的发生发展。     

Frequencies of circulating IL-17-producing CD4+CD161+ T cells and CD4+CD161+ T cells correlate with disease activity in rheumatoid arthritis

Abstract

Objective. Rheumatoid arthritis (RA) is a common autoimmune disease that is primarily driven by effector T cells, particularly Th17 cells, which are mainly contained within CD4+CD161+ T cells. Thus, we aimed to explore whether the frequencies of circulating IL-17-producing CD4+CD161+ T cells and CD4+CD161+ T cells were correlated with RA disease activity.

Methods. The surface phenotype and cytokine production of blood were analyzed by flow cytometry in 52 RA patients and 17 healthy controls. The disease activity was evaluated by the 28-joint disease activity score.

Results. The frequencies of circulating IL-17-producing CD4+CD161+ T cells and CD4+CD161+ T cells were increased in RA patients, and they were elevated in patients with active disease status compared to patients with low disease status. Furthermore, their frequencies were positively correlated with disease activity parameters. Receiver operating characteristic curve analysis revealed that IL-17-producing CD4+CD161+ T cell levels were able to distinguish disease activity with 60.7 % sensitivity and 87.5 % specificity, while CD4+CD161+ T cell levels showed 92.9 % sensitivity and 66.7 % specificity.

Conclusion. These results support the hypothesis that Th17 cells are involved in the pathogenesis of RA and suggest that circulating CD4+CD161+ T cells are a potential biomarker of RA disease activity.     

肺结核患者外周血CD_4~+、CD_8~+T细胞Blimp-1表达下降

目的研究活动性肺结核患者外周血单个核细胞(PBMCs)Blimp-1的表达及临床意义。方法采集31例活动期肺结核患者和45位健康对照组外周血,纯化PBMCs,用结核分枝杆菌ESAT-6和CFP-10混合性抗原肽库刺激,通过细胞表面标记和细胞内细胞因子染色技术,采用流式技术检测CD+4、CD+8T细胞Blimp-1的表达。结果与对照组比较,肺结核患者PBMCs中的CD+4、CD+8T细胞亚群分布出现显著性下降,且肺结核患者CD+4T细胞中Blimp-1的表达比例(%)下降(肺结核组89.5%(83.8%,95.7%),对照组94.5%(89.8%,98.7%),P0.05),且CD+4、CD+8T细胞中Blimp-1的表达量(平均荧光强度)也显著性下降(CD+4T细胞:肺结核组9.28(7.5,18.9),对照组15.4(11,25.4),P0.05);CD+8T细胞:肺结核组9.01(6.08,14.7),对照组14.2(9.53,23.1),P0.05)。结论活动期肺结核CD+4、CD+8T细胞群内Blimp-1的表达下降可能会使效应性和调节性T细胞的分化出现异常。Blimp-1可能参与结核病的疾病进程,这为研究结核病的诊断和治疗提供了线索。     

慢性心力衰竭患者CD4+CD25+调节性T细胞检测及意义

目的:探讨慢性心力衰竭(CHF)患者外周血CD4 CD25 调节性T细胞(Treg)水平及意义。方法:采用流式细胞分析法,检测42例CHF患者(CHF组)和16例正常对照者(对照组)外周血CD4 CD25 Treg/CD4 T细胞比例。结果:CHF患者外周血CD4 CD25 Treg/CD4 T细胞比例[(12.2±3.8)%]显著低于对照组[(16.3±5.2)%]。CD4 CD25 Treg/CD4 T比例在缺血性心脏病者[(12.6±4.1)%]与非缺血性心脏病者(12.0±3.7%)间差异无统计学意义,但心功能NYHA分级Ⅲ~Ⅳ级者[(10.4±3.2)%]比例明显低于Ⅰ~Ⅱ级者[(13.3±3·8)%]。结论:CHF患者外周血Treg比例减少,且与心功能有一定关系。CD4 CD25 Treg比例降低可能打破了外周免疫耐受,参与了心力衰竭的发生发展。     

感染弓形虫小鼠脾脏CD4+CD25+T细胞的变化

目的 观察小鼠感染刚地弓形虫后脾脏CD4⁺CD25⁺调节性T细胞的动态变化。 方法 将28只雌性C57BL/6小鼠随机分为4组，其中3组每鼠腹腔接种弓形虫速殖子悬液200 μl（含弓形虫速殖子5×10⁴个/ml），对照组腹腔接种灭菌PBS 200 μl。分别于弓形虫感染后第2、4和6天取脾，制成单个核细胞，用实时荧光定量PCR检测脾CD4⁺ T细胞Foxp3基因表达水平，流式细胞仪检测脾CD4⁺CD25⁺调节性T细胞占CD4⁺ T细胞的比例，并对CD4⁺CD25⁺调节性T细胞和CD4⁺ T细胞进行绝对计数。 结果 感染后第4和6天，小鼠脾脏CD4⁺ T细胞Foxp3 mRNA相对表达水平分别为 1.89±0.23和1.79±0.24， 均显著高于正常水平（1.00±0.12）（P＜0.01）；CD4⁺CD25⁺调节性T细胞占CD4⁺ T细胞的比例从感染后第2天（15.07%±2.73%）开始上调（P＜0.05），至感染后第4 和6天分别为24.29%±3.19%和19.80%±2.66%，均明显高于正常水平（11.58%±2.04%） （P＜0.01）；脾脏CD4⁺ T细胞占脾细胞的比例及其绝对数量均从感染后第2 天开始降低，至感染后第6 天分别降至5.49%±1.71%和（1.71±0.44）×10⁶ （P＜0.01）。 结论 弓形虫感染导致小鼠脾脏CD4⁺CD25⁺调节性T细胞占CD4⁺ T细胞的比例上调，而脾脏CD4⁺ T细胞的显著减少是促成比例上调的主要原因。     

CD4^＋CD25^＋调节性T细胞在特发性血小板减少性紫癜患者中的变化及意义

目的:通过检测特发性血小板减少性紫癜(ITP)患者治疗前后外周血CD4 CD25 调节性T细胞(regulatory T cell,Treg)的比例及变化规律,探讨Treg细胞在ITP发病中的可能作用。方法:采集30例急、慢性ITP患者治疗前、后和20例正常对照者的外周血标本,流式细胞仪检测Treg细胞的比例及变化,并评价其与血小板计数的相关性。结果:30例ITP患者治疗前Treg细胞的比例为(1.59±0.86)%,明显低于正常对照组(3.87±1.73)%(P<0.01),治疗后其比例显著升高,为(2.51±1.17)%,明显高于治疗前(P<0.01),但仍低于正常对照组(P<0.01);Treg细胞在治疗显效和良效组显著高于进步和无效组(P<0.01),进步组与无效组比较差异无统计学意义(P>0.05);此外治疗前后Treg细胞比例与血小板计数呈显著正相关(P<0.05)。结论:ITP患者外周血Treg细胞比例降低,但随免疫抑制治疗的疗效逐渐升高,提示CD4 CD25 调节性T细胞可能参与了ITP的发病机制。     

Evidence of CD4 + regulatory T cells in the non-obese diabetic male mouse

Summary The NOD mouse, which shows many features of human IDDM, is extensively used to evaluate the role of T lymphocytes in the pathogenesis of autoimmune diabetes. The development of diabetes in this model appears to be controlled by a finely tuned immunoregulatory balance between autoaggressive T cells and regulatory immune phenomena, the disruption of which may result in destruction of insulin-secreting cells. The absolute requirement of sublethal irradiation to permit transfer of the disease to non-diabetic adult syngeneic mice provides indirect evidence for the presence of regulatory T cells in non-diabetic NOD mice. We have previously reported that the reconstitution of irradiated recipients by CD4 + T cells from nondiabetic female NOD mice blocks the transfer of diabetes by spleen cells from diabetic donors. We now report evidence that anti-CD4 monoclonal antibodies can substitute for irradiation in rendering adult NOD male mice susceptible to diabetes transfer by diabetogenic spleen cells. Efficient diabetes transfer can be achieved in non-irradiated adult NOD recipients provided they are thymectomized and CD4 + T-cell depleted prior to the transfer. The role of thymectomy is to limit T cell regeneration after anti-T cell monoclonal antibody challenge. Our data confirm that regulatory CD4 + T-cells, which efficiently counterbalance diabetogenic cells, are present in adult NOD male animals.Abbreviations FITC fluorescein isothiocynate - HBSS Hank's balanced salt solution - IDDM insulin-dependent diabetes mellitus - IL interleukin - NOD non-obese diabetic - TH T helper     

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。     

Consequence of Histoincompatibility beyond GvH-Reaction in Cytomegalovirus Disease Associated with Allogeneic Hematopoietic Cell Transplantation: Change of Paradigm

Hematopoietic cell (HC) transplantation (HCT) is the last resort to cure hematopoietic malignancies that are refractory to standard therapies. Hematoablative treatment aims at wiping out tumor cells as completely as possible to avoid leukemia/lymphoma relapse. This treatment inevitably co-depletes cells of hematopoietic cell lineages, including differentiated cells that constitute the immune system. HCT reconstitutes hematopoiesis and thus, eventually, also antiviral effector cells. In cases of an unrelated donor, that is, in allogeneic HCT, HLA-matching is performed to minimize the risk of graft-versus-host reaction and disease (GvHR/D), but a mismatch in minor histocompatibility antigens (minor HAg) is unavoidable. The transient immunodeficiency in the period between hematoablative treatment and reconstitution by HCT gives latent cytomegalovirus (CMV) the chance to reactivate from latently infected donor HC or from latently infected organs of the recipient, or from both. Clinical experience shows that HLA and/or minor-HAg mismatches increase the risk of complications from CMV. Recent results challenge the widespread, though never proven, view of a mechanistic link between GvHR/D and CMV. Instead, new evidence suggests that histoincompatibility promotes CMV disease by inducing non-cognate transplantation tolerance that inhibits an efficient reconstitution of high-avidity CD8⁺ T cells capable of recognizing and resolving cytopathogenic tissue infection.     

不同免疫抑制诱导治疗对肝移植受者CD4+CD25+high细胞的影响

目的CD4^＋CD25^＋Treg细胞介导的免疫调节对诱导和维持移植物免疫耐受有非常重要的作用，本研究探讨抗胸腺淋巴细胞球蛋白（ATG）和噻呢哌这两种不同作用途径的免疫抑制诱导药物对CD4^＋CD25^＋high／CD4^＋T细胞及其表面标志性因子CTLA-4、Foxp3的影响，为临床合理选择应用免疫诱导药物提供依据。方法选择15例在我院行同种异体肝移植患者，随机分为ATG组（8例）和噻呢哌组（7例），两组除免疫抑制诱导药物不同外，均接受相同治疗。分别于术前、术后3周、6周、8周取血，应用流式细胞仪检测CD4^＋CD25^＋high/CD4^＋T细胞的数量及其表面因子CTLA-4和Foxp3表达状况，比较不同诱导药物对其影响。结果这两种免疫抑制诱导药物对CD4^＋CD25^＋Treg细胞短期内有一定影响，但可逐渐恢复，两者比较，使用ATG后各指标恢复较噻呢哌快，尤其是Foxp3更加明显。结论作为诱导治疗药物，ATG更有利于CD4^＋CD25^＋Treg细胞功能恢复，从而有助于更好形成移植免疫耐受。     

Increased population of CD4(+)CD25(high), regulatory T cells with their higher apoptotic and proliferating status in peripheral blood of acute myeloid leukemia patients

PURPOSE: Regulatory T cells (T-reg) that control harmful autoimmune T cells in the periphery may also suppress the immune response against cancer. In this study we investigated the possible involvement of CD4(+)CD25(high) T-reg in the immune impairment of patients with acute myeloid leukemia (AML). EXPERIMENTAL DESIGN: The frequencies and phenotypes of CD4(+)CD25(high) T cells in the peripheral blood of AML patients were determined by flow cytometry. To assess the functional activity of CD4(+)CD25(high) T cells, CD4(+)CD25(high), and CD4(+)CD25(-) T cells were sorted from peripheral blood mononuclear cells with FACS Vantage. The immunoregulatory properties of CD4(+)CD25(high) and CD4(+)CD25(-) T cells were characterized by proliferation assays and cytokine production assays. In addition, the frequency of apoptotic and proliferating cells in CD4(+)CD25(high) T cells were respectively evaluated by 7AAD and ki67 binding cells using flow cytometry. RESULTS: Compared with healthy controls, AML patients had a higher proportion of CD4(+)CD25(high) T cells in peripheral blood. These cells were CD45-RA(-), CD69(-), CD45-RO(+), CD95(+), and intercellular CTLA-4(+), and secreted low levels of TNF-alpha and IL-10, but no IL-2, IL-4, IL-5, and IFN-gamma. They inhibited the proliferation and cytokine production (IL-2, IFN-gamma) of CD4(+)CD25(-) T cells, but improved IL-10 production under the co-culture of both subsets with stimulation, thus behaving as T-reg. Notably, CD4(+)CD25(high) T cells in AML patients presented significantly higher apoptosis and proliferation than that of healthy individuals. CONCLUSIONS: The frequency of CD4(+)CD25(high) T-reg in peripheral blood in AML patients is significantly higher when compared with healthy individuals, likely due to the increasing proliferation of CD4(+)CD25(high) T cells.