Changes of CD4+CD25+FOXP3 + and CD8+CD28 − regulatory T cells in non-small cell lung cancer patients undergoing surgery

Little is known about the regulatory T cells (Tregs) in the peripheral blood after surgery of non-small cell lung cancer (NSCLC) patients. In this study, we investigated whether CD4+CD25+FOXP3 + and CD8+CD28 − regulatory T cells are decreased in the peripheral blood of NSCLC patients undergoing surgery. The study group (n = 49) comprised NSCLC, and the control group (n = 24) consisted of age- and sex-matched nonmalignant diseases. The prevalence of CD4+CD25+FOXP3 + and CD8+CD28 − Tregs was analyzed using flow cytometry. The study group showed significantly higher percentage of CD4+CD25+FOXP3 + and CD8+CD28 − Tregs than control. The percentage of CD4+CD25+FOXP3 + and CD8+CD28 − Tregs increased with tumor stage. One way ANOVA test shows the significant differences between all subgroups. LSD test shows that there was a statistical significance between each of the two subgroups except stage II in CD4+CD25+FOXP3 + Tregs and control vs. each stage, stage I vs. stage III, and stage IV in CD8+CD28 − Tregs. There is no significant difference among stages II, III, and IV in CD8+CD28 − Tregs. No differences were found between squamous carcinoma and adenocarcinoma. These levels were dropped significantly after operation. Furthermore postoperative Treg percentage in the early stages (stage I and stage II) was not statistically different from that of controls. Postoperative Treg percentage in advanced stage (III + IV) remained above the values shown by controls. Our findings indicate that the percentage of CD4+CD25+FOXP3 + and CD8+CD28 − Tregs correlated with the pathological stage in NSCLC and tumor burden.     

Inhibitor of PI3Kγ ameliorates TNBS-induced colitis in mice by affecting the functional activity of CD4+CD25+FoxP3+ regulatory T cells

BACKGROUND AND PURPOSE

Phosphoinositide 3-kinase-γ (PI3Kγ) is implicated in many pathophysiological conditions, and recent evidence has suggested its involvement in colitis. In the present study, we investigated the effects of AS605240, a relatively selective PI3Kγ inhibitor, in experimental colitis and its underlying mechanisms.

EXPERIMENTAL APPROACH

Acute colitis was induced in mice by treatment with trinitrobenzene sulphonic acid (TNBS), and the effect of AS605240 on colonic injury was assessed. Pro-inflammatory mediators and cytokines were measured by immunohistochemistry, elisa, real time-polymerase chain reaction and flow cytometry.

KEY RESULTS

Oral administration of AS605240 significantly attenuated TNBS-induced acute colitis and diminished the expression of matrix metalloproteinase-9 and vascular endothelial growth factor. The colonic levels and expression of IL-1β, CXCL-1/KC, MIP-2 and TNF-α were also reduced following therapeutic treatment with AS605240. Moreover, AS605240 reduced MIP-2 levels in a culture of neutrophils stimulated with lipopolysaccharide. The mechanisms underlying these actions of AS605240 are related to nuclear factor-κ (NF-κB) inhibition. Importantly, the PI3Kγ inhibitor also up-regulated IL-10, CD25 and FoxP3 expression. In addition, a significant increase in CD25 and FoxP3 expression was found in isolated lamina propria CD4⁺ T cells of AS605240-treated mice. The effect of AS605240 on Treg induction was further confirmed by showing that concomitant in vivo blockade of IL-10R significantly attenuated its therapeutic activity.

CONCLUSIONS AND IMPLICATIONS

These results suggest that AS605240 protects mice against TNBS-induced colitis by inhibiting multiple inflammatory components through the NF-κB pathway while simultaneously inducing an increase in the functional activity of CD4⁺CD25⁺ Treg. Thus, AS605240 may offer a promising new therapeutic strategy for the treatment of inflammatory bowel diseases.     

CD4+ Foxp3+ regulatory T cells induced by TGF-β, IL-2 and all-trans retinoic acid attenuate obliterative bronchiolitis in rat trachea transplantation

Obliterative bronchiolitis (OB) is the major obstacle for long-term allograft survival in lung transplantation, and the underlying mechanism is still not well understood. Regulatory T cells (Tregs) have been shown to be essential in the maintenance of immune tolerance. In this study we investigated the role of Tregs in protecting OB in rat. We show that the combination of TGF-β, Interleukin (IL)-2, and all-trans retinoic acid (atRA) could induce naïve rat CD4⁺CD25⁻ T cells to differentiate into CD4⁺CD25⁺Foxp3⁺ T cells in vitro, and they acquired suppressive function. In a rat orthotopic tracheal transplantation OB model, the adoptive transfer of the induced Tregs reduced symptoms of airway obliteration and fibrication of grafts when compared with adoptive transfer of control cells without suppressive property. Moreover, recipients treated with the induced Tregs secreted high level of immunosuppressive cytokine TGF-β and IL-10, and low level of pro-inflammatory cytokines IL-17, IFN-γ, IL-6, and MCP-1, and had fewer effector T cells including Th17 cells and Th1 cells in the graft. Taken together, these findings suggest that in vitro induced Tregs by the combination of TGF-β, IL-2, and atRA are effective in protecting rat trachea allograft rejection through the inhibition of effector T cells and their function. These datas implicate new therapies to prevent OB and allograft rejection in human lung transplantation.     

CD4+CD25+调节性T细胞与儿科疾病

古希腊特尔斐阿波罗神庙上镌刻着一句铭言:Gnothi Seauton(英文为know thyself)即"认识自己"."认识自己"已成为免疫学家广为认可的定律:机体免疫系统首先必须识别自身的抗原,产生无反应性,再针对外来抗原产生免疫应答,即"识别自身,排斥异己".     

Effect of RAGE and its ligands on CD4+ T cells北大核心CSCD

RAGE (receptor for advanced glycation end products) is a multiligand receptor on the cell surface. Ligand-RAGE interactions activate several signal transduction pathways that propagate cellular oxidative stress and inflammatory response. RAGE expressed on the CD4+ T cells has been identified as a central transduction receptor which affects the activation, proliferation, migration and differentiation of the cells. In addition, blockade of RAGE suppressed the development of multiple immune-related disorders mediated by CD4+ T cells. These studies highlight the importance of RAGE and its ligands for CD4+ T cells. This article briefly reviews the role of RAGE and its ligands on the proliferation, migration and differentiation of CD4+ T cells and summarizes the related research progress.     

Astilbin promotes the induction of regulatory NK1.1− CD4+ NKG2D+ T cells through the PI3K,STAT3, and MAPK signaling pathways

Astilbin is a potential agent for autoimmune and inflammatory diseases and has a protective effect in mice with DSS-induced colitis. NK1.1⁻ CD4⁺ NKG2D⁺ T cells are a subpopulation of regulatory T cells that produce TGF-β1 and IL-10. Whether astilbin directly promotes the induction of NK1.1⁻ CD4⁺ NKG2D⁺ T cells and whether these astilbin-stimulated T cells exert an immune-regulatory role remain unclear. Here, we show that astilbin efficiently induces the production of NK1.1⁻ CD4⁺ NKG2D⁺ T cells with high expressions of TGF-β1, IL-10, CCR6, and CCR9 in a dose-dependent manner ex vivo. These regulatory T cells also substantially inhibit the activities of CD8⁺ T cells and macrophages. Intraperitoneal injection of astilbin ameliorates the severity of colitis with an increase in the frequency of NK1.1⁻ CD4⁺ NKG2D⁺ T cells in the colon tissue of DSS-treated mice. Moreover, adoptive transfer of NK1.1⁻ CD4⁺ NKG2D⁺ T cells induced by astilbin remarkably protects against the onset of DSS-induced colitis. Finally, the PI3K, STAT3, and MAPK signaling pathways are involved in the induction of NK1.1⁻ CD4⁺ NKG2D⁺ T cells by astilbin. Taken together, our study elucidates a new immune-regulatory mechanism of astilbin by inducing the regulatory NK1.1⁻ CD4⁺ NKG2D⁺ T cells and indicates a potential clinical use of astilbin for patients with inflammatory bowel diseases.     

CD4+CD25+T细胞在自身免疫性疾病中的作用

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细胞的减少或功能下降可能导致自身免疫性疾病的发生。近年来CD~ CD25~ T细胞与自身免疫性疾病的关系得到了广泛的研究,为后者的治疗提供了新的思路和方法。     

狼疮性肾炎患儿外周血CD4+CD25+调节性T细胞的变化

目的 探讨狼疮性肾炎(LN)患儿外周血CD4+CD25+调节性T细胞(Tregs)的变化及意义.方法 采用流式细胞术检测30例LN患JL(LN组)和30例健康儿童(对照组)外周血CD4+CD25+调节性T细胞百分比,并分析其与24-h尿微量白蛋白(UMA)及狼疮活动指数(SLE-DAI)的关系.结果 LN患儿外周血中CD4+CD25+Tregs明显低于对照组(P<0.01);CD4+CD25+Tregs 与24-h UMA呈显著负相关,与SLE-DAI呈等级负相关.结论 LN患儿外周血CD4+CD25+Tregs百分比异常降低可能参与LN的起病与发展.CD4+CD25+Tregs百分比与24-h UMA呈显著负相关,与SLE-DAI呈等级负相关,提示可以作为监测LN患儿病情及预后的指标.     

CD4+CD25+调节性T细胞在Graves眼病中的免疫调节作用

CD4+CD25+调节性T细胞(Treg)具有维持自身免疫耐受和调节免疫应答的功能,其功能紊乱或数量下降是导致自身免疫性疾病的重要原因之一.Graves眼病(graves ophthalmopathy,GO)是自身免疫性疾病,目前其确切的病因及发病机制未完全明确.大量研究表明Treg与自身免疫性甲状腺疾病相关,但Treg在GO发病机制中的作用研究不多.本文将对Treg在GO中的免疫调节作用作一综述.     

探析系统性红斑狼疮患者CD4+CD25+调节性T细胞的变化

本文首先使用流式细胞术检测xx例SLE患者及XX名正常人,对照两个实验组的外周血中CD4+CD25+调节性T细胞和CD4+CD25+T细胞占CD4+T细胞的比率,深入分析CD4+CD25+调节性T细胞与SLE之间的关系,通过对照实现发现活动性SLE患者外周血中CD4+CD25+调节性T细胞及CD4+CD25+T细胞比例低于正常人,而且与红斑狼疮的SLEDAI指数呈现负相关等实验结果。希望通过本文的研究能够更加清楚的了解系统性红斑狼疮患者CD4+CD25+调节性T细胞的变化以及与SLE发病之间的关系,从而为后期的临床研究治疗提供参考。     

CD4+CD25+Foxp3+调节性T细胞与慢性乙型肝炎病毒感染的关系

目的 探讨调节性T细胞（Treg）在慢性乙型肝炎病毒感染中的免疫调节作用。方法 采用流式细胞术检测慢性活动性肝炎患者、乙型肝炎病毒携带者、乙型肝炎恢复者及健康对照者外周血CIN^＋T细胞中的CIN^＋CD25^＋Foxp3^＋调节性T细胞的比例。采用免疫组织化学法检测肝组织中Foxp3的表达。统计分析外周血中CIN^＋CD25^＋Foxp3^＋调节性T细胞的比例数与血清HBeAg和HBVDNA含量的关系。结果 外周血CIN^＋T细胞中CIN^＋CD25^＋Foxp3^＋调节性T细胞的比例数在慢性活动型肝炎组和乙型肝炎病毒携带组均高于健康对照组（P〈0．05），乙型肝炎病毒携带者组高于乙型肝炎恢复组（P〈0．05）。Foxp3在慢性活动型肝炎组肝组织中的阳性率和阳性细胞数均高于乙型肝炎病毒携带者组（P〈0．05）。外周血HBeAg（＋）患者Treg的比例数高于血清HBeAg（-）患者Treg的比例数（t=1．67．P〈0．05）。患者外周血CIN^＋CD25^＋Foxp3^＋Treg的比例数与血清HBV DNA含量呈正相关（r=0．56，P〈0．01）。结论 CIN^＋CD25^＋Foxp3^＋调节性T细胞可能与乙型肝炎病毒感染慢性化及乙型肝炎病毒的清除有关。     

孕妇外周血CD4+CD25+调节性T细胞对子痫前期的预测

目的:探讨孕妇外周血CD4+ CD225+调节性T细胞(CD4 CD25+ Tregs)对子痫前期的预测价值.方法:选取190例于我院产前常规孕期体检及分娩的孕产妇作为研究对象,按孕产妇是否发生子痫前期分为子痫前期组及正常对照组,采用流式细胞仪测定各孕妇20～24周外周血单个核细胞(PBMC)中CD4T细胞及CD4 CD25+ Tregs的比率,并随访至分娩.采用磁珠分选技术分选随访期间确诊子痫前期的患者外周血PBMC中CD4 CD25+ Tregs和CD4CD25T细胞,酶联免疫仪检测CD4 CD25+ Tregs对CD4CD25T细胞增殖的抑制作用,并与正常孕妇组对比.结果:①随访情况.190例孕产妇妊娠期内有15例发展为子痫前期,其余175例为正常分娩,2组在剖宫产率、胎儿心率异常率、新生儿1 min及5 min的Apgar评分有显著性差异(P＜0.05).②CD4 CD25+ Tregs的数量.子痫前期组和正常对照组外周血PBMC中CD4T细胞比率分别为34.21％±6.92％和35.72％±7.45％,2组比较无显著性差异(P＞0.05).子痫前期组外周血PBMC中CD4 CD25+ Tregs占CD4T细胞的比率为6.71％±2.21％,明显低于正常对照组的12.01％±2.98％(P＜0.05).③CD4 CD25+ Tregs的抑制功能.子痫前期组CD4 CD25+ Tregs对CD4 CD25-T细胞增殖的抑制百分率为57.56％±9.47％,正常孕妇组为78.27％±12.43％,2组比较有显著性差异(P＜0.05).④CD4 CD25+ Tregs的预测性.以CD4+ CD25+ Trges数量变化预测子痫前期的ROC曲线下面积为0.913,Tregs的最佳截断点为6.605％,预测子痫前期的敏感度86.7％、特异度82.85％.结论:孕妇妊娠中期外周血CD4 CD25+ Tregs数量减少和(或)抑制功能下降与子痫前期的发生相关,可作为子痫前期的预测性指标.     

无症状期艾滋病HIV感染者CD+4 CD+8 T淋巴细胞检测结果分析

目的分析本地区人类免疫缺陷病毒(HIV)感染者免疫力被破坏情况,制订相应的艾滋病(AIDS)防治方案.方法对1344例无症状HIV感染者进行CD+4、CD+8 T淋巴细胞检测.结果发现18例免疫力极度低下(CD+4＜30个/mm3)的处于无症状期的HIV感染者,其CD+8T淋巴细胞值≥(400～800个/mm3).结论无症状的HIV感染者中存在着免疫力极度低下者,由于高水平的CD+8T淋巴细胞的抗病毒作用而使之处于无症状期,但其免疫系统已严重受损,任何机会性感染都会诱发他们发展为AIDS.测定其CD+4、CD+8T淋细胞作为预见HIV感染状态和进展为AIDS的重要参考指标,具有不可替代的作用.     

CD4+CD25+调节性T细胞在肿瘤免疫中的意义及研究进展

肿瘤的发生发展与宿主的免疫状态密切相关,宿主抗肿瘤反应以细胞免疫为主,多种肿瘤患者存在T淋巴细胞亚群状态异常和比例失调.CD4+CD25+调节性T细胞(Tregulatory cells,Treg)近年来引起国内外学者的广泛关注,越来越多的研究表明,Treg参与肿瘤的免疫逃逸,使肿瘤特异性T效应细胞不能扩增到一定水平以根除肿瘤[1,2].现将CD4+CD25+Treg在肿瘤免疫中的意义及研究进展综述如下.     

肺癌患者外周血CD4+CD25+调节性T细胞的检测及其临床意义

目的 探讨检测肺癌患者手术前后外周血CD4+CD25+调节性T细胞的临床意义.方法 原发性肺癌患者43例(肺癌组),健康体检者20例(健康对照组).应用流式细胞术检测其外周血CD4+CD25+调节性T细胞的水平.结果 肺癌组患者手术前外周血CD4+CD25+调节性T细胞表达高于健康对照组(P<0.01);肺癌组患者术后30 d时外周血CD4+CD25+调节性T细胞水平较术前明显下降(P<0.05).结论 肺癌患者外周血CD4+CD25+调节性T细胞的水平增高;肺癌患者术后外周血CD4+CD25+调节性T细胞的水平下调,提示术后机体抗肿瘤免疫功能有了一定程度恢复.     

无症状期艾滋病HIV感染者CD+4 CD+8 T淋巴细胞检测结果分析

目的分析本地区人类免疫缺陷病毒(HIV)感染者免疫力被破坏情况,制订相应的艾滋病(AIDS)防治方案.方法对1344例无症状HIV感染者进行CD+4、CD+8 T淋巴细胞检测.结果发现18例免疫力极度低下(CD+4＜30个/mm3)的处于无症状期的HIV感染者,其CD+8T淋巴细胞值≥(400～800个/mm3).结论无症状的HIV感染者中存在着免疫力极度低下者,由于高水平的CD+8T淋巴细胞的抗病毒作用而使之处于无症状期,但其免疫系统已严重受损,任何机会性感染都会诱发他们发展为AIDS.测定其CD+4、CD+8T淋细胞作为预见HIV感染状态和进展为AIDS的重要参考指标,具有不可替代的作用.     

慢性乙型肝炎患者血CD4+CD25+调节性T细胞检测的临床意义

目的 探讨慢性乙型肝炎患者外周血CD4+CD25+调节性T细胞(CD4+ CD25+ Treg)检测的临床意义。方法 慢性HBV感染者48例（慢性HBV携带者10例为慢性HBV携带者组、慢性乙型肝炎18例慢性乙型肝炎组和乙肝肝硬化为乙肝肝硬化组20例）,以流式细胞仪检测血CD4+CD25+Treg细胞频率,实时荧光定量聚合酶链反应检测血HBV DNA载量。结果 血CD4+CD25+Treg细胞百分率：慢性HBV携带者组为(6.72±2.60)％、慢性乙型肝炎组为(8.56±3.12)％、乙肝肝硬化组为(11.59±4.34)％,组间差异有统计学意义（均P＜0.05）。血HBV DNA载量：慢性HBV携带者组为1.7 ×106拷贝/ml、慢性乙型肝炎组为4.3 ×105拷贝/ml、乙肝肝硬化组为6.8 ×104拷贝/ml,组间差异有统计学意义(P＜0.01);慢性肝病患者血CD4+CD25+调节性T细胞百分率与HBV DNA滴度正相关。结论 慢性肝病患者血Treg细胞频率与HBVDNA滴度正相关,提示Treg细胞在慢性乙型肝炎致病机制中起重要作用。     

CD4+CD25+调节性T细胞在多种类型疫苗中作用的研究进展

CD4⁺CD25⁺ 调节性T细胞具有免疫抑制作用。CD4⁺CD25⁺ 调节性T细胞可由多种类型肿瘤、病原体诱导产生。一方面抑制炎症,防止机体组织损伤;另一方面阻碍机体清除肿瘤细胞和病原体,有利于肿瘤和病原体逃避宿主免疫攻击。使用抗体阻断CD4⁺CD25⁺ 调节性T细胞或干扰其抑制功能则利于机体清除肿瘤和病原体。同样,多种类型疫苗可诱导宿主产生CD4⁺CD25⁺ 调节性T细胞,因而抑制了疫苗引起的免疫反应。使用抗体如抗CD25单克隆抗体等封闭CD4⁺CD25⁺ 调节性T细胞或者抑制其分泌的细胞因子如白细胞介素-10(IL-10)、转化生长因子-β(TGF-β),可增强疫苗的免疫保护效果,从而为寻找更有效的疫苗提供新的思路。