CD+4 CD+25调节性T细胞抑制持续性丙型肝炎病毒感染患者CD+4T细胞反应

目的探讨CD+4 CD+25调节性T细胞(CD+4 CD+25Treg细胞)在持续性HCV感染患者CD+4 T细胞下调中的意义.方法流式细胞术检测慢性丙型肝炎患者外周血中CD+4 CD+25Treg细胞的数量以及细胞内因子的合成;与正常人或患者CD+4 CD-25 T细胞共同培养,检测其抑制功能;RT-PCR检测Foxp3的mRNA表达.结果 CD+4 CD+25Treg细胞约占慢性丙型肝炎患者外周血中CD+4 T细胞的(13.5±1.8)%,高于正常对照(5.3±0.8)% (P=0.004);主要合成IL-10,高表达Foxp3;CD+4 CD+25Treg细胞显著抑制CD+4 T细胞的增殖,以及合成IFNγ,并且抑制活性较正常人增高(P=0.034),这种作用不依赖IL-10和转化生长因子β.结论持续性HCV感染患者CD+4 CD+25Treg细胞表达增加,抑制活性增强,特异性抑制Th1反应.     

CD4+CD25+T细胞与支气管哮喘

本文就CD4^＋CD25^＋T细胞的调节机制，CD4^＋CD25^＋T细胞与变态反应的关系，以及CD4^＋CD25^＋T细胞在支气管哮喘发病机制中的作用作一综述。     

CD4+CD25+调节性T细胞对慢性丙型肝炎患者病毒特异性CD8+T细胞的抑制作用

HCV感染是严重危害人民健康的传染病，易发展成慢性丙型肝炎、肝硬化，且与原发性肝癌密切相关。HCV持续感染的一个重要原因是HCV特异性CD8^＋T细胞数量及功能缺陷，表现在体外增殖能力下降和IFN-γ分泌水平降低。CD4^＋CD25^＋调节性T细胞（T regulatory cells，Treg）主要在机体免疫系统中发挥负向调节作用，在移植物抗宿主病、自身免疫病、过敏性疾病等的发病机制和临床治疗中有潜在应用价值。已有研究表明，     

关于CD4+ CD25+调节性T细胞的研究

ＣＤ4 + 、ＣＤ2 5 + 细胞同时具有无能性和抑制性 ,是一类存在于动物和人类体内的调节性Ｔ细胞。近来研究证实生后第 3天切除胸腺的小鼠缺乏ＣＤ4 + 、ＣＤ2 5 + Ｔ细胞 ,而其他Ｔ细胞则不受影响 ;从胸腺细胞和成熟个体的脾细胞中分离纯化小鼠用抗ＣＤ2 5抗体去除ＣＤ4 + 、ＣＤ2 5 + Ｔ细胞后则易患自身免疫病 ;裸鼠过继转移去除ＣＤ4 + 、ＣＤ2 5 + Ｔ细胞的ＣＤ4 + Ｔ细胞后所发生自身免疫病 ,且能被过继转移ＣＤ4 + 、ＣＤ2 5 + Ｔ细胞所治愈。这些研究证据表明ＣＤ4 + 、ＣＤ2 5 + Ｔ细胞是免疫调节性Ｔ细胞。ＣＤ2 5是白细胞介素 (Ｉ…     

肝癌微环境中CD4+CD25+调节性T细胞与T细胞免疫的关系

目的 了解肝细胞癌组织CD4 CD25 调节性T细胞(以下简写Treg)与肿瘤微环境T细胞免疫的关系.方法 对52例肝癌组织和癌旁组织用CD4、CD25双重酶标免疫组化染色和用CD8En Vision法染色,对癌组织中Treg细胞和CD4 T、CD8 T、CD4 T/CD8 T比值进行相关性分析.结果 肝癌以及癌旁组织中Treg细胞单个高倍视野平均数分别为7.6308±2.8368、5.1654±1.6718;两组比较有显著差异,P=0.000;肝癌组织中Treg细胞的数量与其浸润性CD4 T淋巴细胞的数量以及CD4 T/CD8 T比值呈显著负相关,r=-0.538,P=0.014;r=-0.545,P=0.000,与浸润性CD8 T淋巴细胞的数量分布无明显相关性,r=-0.403,P=0.078.结论 Treg在肝癌微环境中可能通过细胞接触的方式抑制CD4 T淋巴细胞的增殖来抑制肿瘤局部免疫,使肿瘤细胞逃避免疫监视.因此除去或减少肝癌微环境中的Treg细胞有利于提高肿瘤的免疫治疗效果.     

CD4+CD25+T细胞--一种新发现的免疫调节细胞

CD4 CD25 T细胞是CD4 T细胞的一个亚型,在机体内起免疫调节作用。本文对它的生物学活性及它在肿瘤、自身免疫性疾病、移植免疫、感染性疾病及病毒性肝炎方面的相关研究作一综述。     

CD4+CD25+调节性T细胞——免疫治疗新策略

1995年日本学者Sakaguchi等[1]首次证实外周血中CD4+T细胞中5%～10%的CD4+CD25+T细胞具有免疫抑制功能,它们能预防和阻止自身免疫病的发生发展,这群细胞被定义为CD4+CD25+调节性T细胞(regulatory T cells,Treg).近十多年对Treg在自身免疫病发病中的作用及机制进行了深入研究,发现免疫病治疗后Treg治疗免疫病具有广阔应用前景.     

CD4+CD25+调节性T细胞与支气管哮喘

支气管哮喘是一种常见的慢性呼吸道疾病,其免疫发病机制尚不十分清楚。CD4 CD25 调节性T细胞是一种特殊的调节性T细胞,参与自身免疫调节,维持自身免疫耐受。本文就CD4 CD25 调节性T细胞的特性及与支气管哮喘的发病机制、治疗、预后的研究进展做一综述。     

CD4+CD25+调节性T细胞与移植免疫耐受

现阶段,器官移植是肝功能衰竭、肾功能衰竭及糖尿病等终末期疾病唯一的治愈途径,虽然临床移植技术取得了很大进步,但仍有两个重大问题阻碍了移植物的长期存活:一是供受者组织相容性基因的多态性使得移植物几乎是毫无例外地发生排斥反应,因此,患者终身服用免疫抑制药物来预防这种排斥反应的发生.     

免疫衰老与CD4+CD25+调节性T细胞

老年人免疫功能下降,机体抵抗力降低,易患肿瘤、感染和自身免疫性疾病等多种老年性疾病,而免疫衰老在该过程中发挥着重要的作用。CD4^＋ CD25^＋调节性T细胞最显著的功能特征是免疫无能性和免疫抑制性,因此它与免疫衰老之间可能存在某种联系。我们对免疫衰老与CD4^＋CD25^＋调节性T细胞之间的关系和研究进展进行了综述。     

CD25+CD4+ T cells contribute to the control of memory CD8+ T cells

Previously we demonstrated that IL-15 and IL-2 control the number of memory CD8+ T cells in mice. IL-15 induces, and IL-2 suppresses the division of these cells. Here we show that CD25+CD4+ regulatory T cells play an important role in the IL-2-mediated control of memory phenotype CD8+ T cell number. In animals, the numbers of CD25+CD4+ T cells were inversely correlated with the numbers of memory phenotype CD8+ T cells with age. Treatment with anti-IL-2 caused CD25+CD4+ T cells to disappear and, concurrently, increased the numbers of memory phenotype CD8+ T cells. This increase in the numbers of CD8+ memory phenotype T cells was not manifest in animals lacking CD4+ cells. Importantly, adoptive transfer of CD25+CD4+ T cells significantly reduced division of memory phenotype CD8+ T cells. Thus, we conclude that CD25+CD4+ T cells are involved in the IL-2-mediated inhibition of memory CD8+ T cell division and that IL-2 controls memory phenotype CD8+ T cell numbers at least in part through maintenance of the CD25+CD4+ T cell population.     

Activated T cells and cytokine-induced CD3+CD56+ killer cells

 Over the past two decades, attempts have been made to develop immunotherapy for patients with cancer. A significant obstacle to the development of successful adoptive immunotherapy has been the availability of appropriate cytotoxic cells. Immunologic effector cells such as lymphokine-activated killer (LAK) cells, activated T cells such as tumor-infiltrating lymphocytes (TILs), and cytokine-induced killer (CIK) cells may be suitable to remove residual tumor cells. Received: 7 October 1996 / Accepted: 13 November 1996     

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.     

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。     

CD4+CD25+ T regulatory cells control anti-islet CD8+ T cells through TGF-beta-TGF-beta receptor interactions in type 1 diabetes

Pancreatic lymph node-derived CD4+CD25+ T regulatory (Treg) cells inhibit in situ differentiation of islet-reactive CD8+ T cells into cytotoxic T lymphocytes, thereby preventing diabetes progression. The mechanism by which these Treg cells suppress anti-islet CD8+ T cells is unknown. Here, we show by using a CD8+ T cell-mediated model of type 1 diabetes that transforming growth factor (TGF)-beta-TGF-beta receptor signals are critical for CD4+CD25+ Treg cell regulation of autoreactive islet-specific cytotoxic T lymphocytes. Transgenic expression of tumor necrosis factor alpha from birth to 25 days of age in the islets of B6 mice that constitutively express CD80 on their beta cells results in accumulation of CD4+CD25+TGF-beta+ cells exclusively in the islets and pancreatic lymph nodes, which delays diabetes progression. In contrast, expression of tumor necrosis factor alpha until 28 days of age prevents islet accumulation of CD4+CD25+TGF-beta+ Treg cells, resulting in acceleration to diabetes. Furthermore, adoptive transfer experiments demonstrated that CD4+CD25+ Treg cells could not control na?ve or activated islet-reactive CD8+ T cells bearing a dominant negative TGF-beta receptor type II. Our data demonstrate that, in vivo, TGF-beta signaling in CD8+ T cells is critical for CD4+CD25+ Treg cell suppression of islet-reactive CD8+ T cells in type 1 diabetes.     

CD8+ T cells control the TH phenotype of MBP-reactive CD4+ T cells in EAE mice

Trimolecular interactions between the T cell antigen receptor and MHC/peptide complexes, together with costimulatory molecules and cytokines, control the initial activation of naive T cells and determine whether the helper precursor cell differentiates into either T helper (TH)1 or TH2 effector cells. We now present evidence that regulatory CD8(+) T cells provide another level of control of TH phenotype during further evolution of immune responses. These regulatory CD8(+) T cells are induced by antigen-triggered CD4(+) TH1 cells during T cell vaccination and, in vitro, distinguish mature TH1 from TH2 cells in a T cell antigen receptor Vbeta-specific and Qa-1-restricted manner. In vivo, protection from experimental autoimmune encephalomyelitis (EAE) induced by T cell vaccination depends on CD8(+) T cells, and myelin basic protein-reactive TH1 Vbeta8(+) clones, but not TH2 Vbeta8(+) clones, used as vaccine T cells, protect animals from subsequent induction of EAE. Moreover, in vivo depletion of CD8(+) T cells during the first episode of EAE results in skewing of the TH phenotype toward TH1 upon secondary myelin basic protein stimulation. These data provide evidence that CD8(+) T cells control autoimmune responses, in part, by regulating the TH phenotype of self-reactive CD4(+) T cells.     

Circulating CD4+CD25+ T cells in rheumatic mitral stenosis

BACKGROUND AND AIM OF THE STUDY: Autoimmunity plays an essential role in the pathogenesis of rheumatic heart disease. Although the ongoing rheumatic process has been demonstrated with high levels of inflammatory markers, the cellular mechanism(s) of autoimmunity have not yet been investigated. The study aim was to examine levels of circulating CD4+CD25+ T cells in patients with rheumatic mitral stenosis, and to evaluate the relationship between regulatory CD4+CD25+ T-cell count and clinical and echocardiographic measures. METHODS: A total of 42 patients with mitral stenosis was enrolled into the study, and 27 normal age- and gender-matched healthy subjects served as controls. All patients and controls underwent clinical, electrocardiographic, echocardiographic and laboratory evaluation. T-cell levels were determined with flow cytometry using monoclonal fluorescein isothiocyanate-labeled anti-CD4 and phycoerythrin-labeled anti-CD25 antibodies. RESULTS: The circulating CD4+CD25+ T-cell count was significantly lower in patients with mitral stenosis than in controls (231 +/- 120 versus 372 +/- 180 per mm3; p = 0.001). The percentage ratio of CD4+CD25+ T cells to total leukocytes and lymphocytes was significantly lower in patients with mitral stenosis than in controls (2.9 +/- 1.5 versus 5.2 +/- 2.1; p < 0.001, and 11.2 +/- 5.6 versus 14.8 +/- 5.6; p = 0.011, respectively). In addition, a significant negative correlation was identified between the erythrocyte sedimentation rate and circulating CD4+CD25+ T-cell count (Spearman rho = -0.414; p = 0.006). No correlation was found between CD4+CD25+ T-cell count and clinical and echocardiographic parameters in patients with mitral stenosis. CONCLUSION: A decrease in CD4+CD25+ T cell numbers in mitral stenosis patients might suggest a role for cellular autoimmunity in a smoldering rheumatic process.