CTLA4-Ig对老年支气管哮喘病人CD4+ CD45 RO+ T细胞功能的影响

目的研究老年支气管哮喘病人周围血CD4 CD45RO T细胞表达IL-4及IL-13的情况及CTLA4-Ig对其影响。方法用ELISA方法测定老年支气管哮喘病人CD4 CD45RO T细胞产生IL-4和IL-13的水平及CTLA4-Ig对其影响。结果老年支气管哮喘病人CD4 CD45RO T细胞分泌IL-4、IL-13增多,IL-13增多较IL-4更为明显(P<0.01),CTLA4-Ig可有效抑制老年哮喘病人CD4 CD45RO T细胞分泌IL-4和IL-13(P<0.01)。结论CD4 CD45RO T细胞产生的IL-4和IL-13在老年哮喘发病中起重要作用,CTLA4-Ig可有效抑制IL-4和IL-13的分泌。     

白介素23受体在支气管哮喘小鼠脾源性CD4^＋T细胞中的表达及意义

-23R）的表达及在哮喘发病中的作用。方法建立急性哮喘小鼠模型,免疫磁珠分离小鼠脾源性CD4^＋T细胞,培养24h后,检测CD4^＋T细胞表面IL-23R的表达、Th17细胞的阳性率及细胞培养上清液中的IL-17水平。结果哮喘小鼠脾脏CD4^＋T细胞表面IL-23R的表达明显高于正常组（P〈0．01）;哮喘小鼠脾脏CD4^＋T细胞中Th17细胞的阳性率明显高于正常组（P〈0．01）;哮喘小鼠脾脏CD4^＋T细胞分泌IL-17浓度明显高于正常组（P〈O．01）;小鼠脾脏CD4^＋T细胞表面IL-23R的表达与Th17细胞的阳性率和IL-17的浓度呈正相关。结论IL-23R在急性哮喘的发病机制中可能起重要作用。     

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。     

抗人细胞毒T淋巴细胞相关抗原4单克隆抗体对特应性支气管哮喘患者记忆性T淋巴细胞功能的影响

细胞毒T淋巴细胞相关抗原4（CTLA4）可以抑制变应原诱导的T淋巴细胞增殖和细胞因子的产生。而记忆性T淋巴细胞（CD45^＋RO^＋T淋巴细胞）在特应性支气管哮喘（简称哮喘）发病中起着重要作用。我们通过CTLA4对哮喘患者CD45^＋RO^＋T淋巴细胞的负向调控作用进行初步探讨。     

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。     

多发性骨髓瘤患者外周血CD4^＋CD25^high调节性T细胞的变化及意义

目的：通过分析CD4^＋CD25^high曲调节性T细胞（Tregs）在不同分期多发性骨髓瘤（MM）患者外周血中的变化和临床意义,初步探讨MM患者的免疫抑制机制。方法：流式细胞术检测40例MM患者及20例健康志愿者外周血T淋巴细胞亚群、NK细胞及CD4^＋CD25^highghT细胞水平,并进行分层分析。结果：①虽然Ⅱ期MM患者CD3^＋、CD4^＋T细胞与对照组比较差异无统计学意义（P〉0．05）,但CD8^＋T细胞明显升高,CD4／CD8明显降低,均差异有统计学意义（均P〈0．05）;随疾病进展至Ⅲ期,CD3^＋、CD4^＋T细胞及CD4／CD8均明显降低,CD8^＋T细胞明显升高,差异有统计学意义（P〈0．01）;各期NK细胞比例与对照组接近（P〉0．05）。②MM患者各期CD4^＋CD25^highT细胞占总CD4^＋T细胞的比例均高于正常对照组,差异有统计学意义（P〈0．01）。进一步分层分析发现,随疾病进展MM患者CD4^＋CD25^high调节T细胞逐渐增高,Ⅲ期增高最为显著（P〈0．05）。结论：MM患者存在细胞免疫功能异常,CD4^＋CD25^highT细胞在其外周血中比例明显升高,且与疾病进展密切相关,这将为免疫治疗MM提供新的参考。     

CD4^＋CD25^＋T细胞与免疫性疾病

90年代初，Sakaguchi和助手研究T细胞介导的免疫抑制，表明小部分（约10％）CD4^＋T细胞组成性表达IL-2（CD25），是体内控制自身反应T细胞的关键。剔除了CD4^＋CD25^＋T淋巴细胞的小鼠CD4^＋T淋巴细胞输注到无胸腺的裸鼠后，     

抗CD3单克隆抗体对支气管哮喘患者CD4＋CD25＋T细胞凋亡和自噬的影响

目的探讨抗CD3单克隆抗体对分离培养的支气管哮喘（简称哮喘）患者外周血CD4＋CD25＋T细胞凋亡和自噬及其分泌的代表性因子转化生长因子p（TGF—β）的影响。方法采用密度梯度离心法及尼龙棉柱法分离32例哮喘患者（哮喘组）及30名健康者（对照组）外周血T细胞,磁性细胞分离器分离得到CD4＋CD25＋T细胞,分别利用电镜及流式细胞仪观察、检测抗CD3单克隆抗体干预72h的细胞凋亡率、自噬率。用EI,ISA法检测细胞培养上清液中细胞因子TGF-β的水平。结果抗CD3单克隆抗体干预72h后两组外周血CD4＋CD25＋T细胞凋亡率、自噬率及TGF-β均增加（P值均〈0．01）,但哮喘组凋亡率、自噬率均低于健康对照组（P值均〈0．01）;两组间 TGF-β水平无显著差异（P〉0．01）。哮喘组外周虹CD4＋CD25＋T调节细胞在CD3单克隆抗体的干预下自噬与TGF-β的分泌呈显著负相关（r=-0．38,P〈0．01）。结论抗CD3单克隆抗体可促进CD4＋CD25＋T细胞凋亡和自噬及TGF-β分泌。     

CD4＋CD25＋调节性T细胞与支气管哮喘的研究进展

支气管哮喘（简称哮喘）是一种气道慢性过敏反应炎症性疾病,表现为反复发作性喘息、胸闷和咳嗽。近年来CD4＋CD25＋调节性T细胞在哮喘发病机制中的作用及其在哮喘治疗中的应用越来越受到人们的关注。现将CD4＋CD25＋调节性T细胞与哮喘的最新研究进展作一综述。     

诱导缓解治疗对系统性红斑狼疮患者外周血CD4^＋CD25^＋T细胞表达的影响

目的探讨CD4^＋CD25^＋调节性T细胞在系统性红斑狼疮（SLE）患者诱导缓解治疗前后外周血的表达及其临床意义。方法入选28例SLE患者和15例正常对照者（对照组）。用流式细胞仪检测SLE患者和对照组的外周血CD4^＋CD25^＋T细胞阳性率。结果SLE患者在诱导缓解治疗前后CD4^＋CD25^＋调节性T细胞比率均低于对照组（P〈0．05）;诱导缓解治疗后患者外周血CD4^＋CD25^＋调节性T细胞比率较治疗前回升,两者间比较无统计学意义（P〉0．05）;SLE合并肾损害者CD4^＋CD25^＋T细胞比率显著低于未合并肾损害者（P〈0．05）。结论SLE患者外周血CD4^＋CD25^＋调节性T细胞数量显著低于正常人,合并肾损害者更明显,且CD4^＋CD25^＋T细胞比率和狼疮活动性指数之间存在相关性。诱导缓解治疗上调了患者外周血CD4^＋CD25^＋T细胞的数量。     

Precommitment of CD4+CD8+ thymocytes to either CD4 or CD8 lineages.

CD4+ and CD8+ mature T cells arise from CD4+CD8+ precursors in the thymus. During this process, cells expressing T-cell receptors (TCRs) reactive with self major histocompatibility complex (MHC) class I or II molecules are positively selected to the CD8 or CD4 lineage, respectively. It is controversial whether lineage commitment of CD4+CD8+ thymocytes is controlled directly by TCR specificity for MHC (instructional model) or, alternatively, by processes that operate independently of TCR specificity (stochastic model). We show here that CD4+CD8+ thymocytes bearing a MHC class I-restricted transgenic TCR can be subject to two alternative developmental fates. One population of CD4+CD8+ cells is positively selected by MHC class I molecules to the CD8 lineage as expected, whereas the other CD4+CD8+ population rearranges endogenous TCR genes and is positively selected by MHC class II molecules to the CD4 lineage. Blocking TCR-MHC class II interactions in vivo does not interfere with the generation of CD4+CD8+ cells expressing endogenous TCRs but does prevent their subsequent maturation to CD4+ cells. These data support a version of the stochastic model in which CD4+CD8+ thymocytes are precommitted to the CD4 or CD8 lineage independently of TCR specificity for MHC and prior to positive selection.     

De novo generation of antigen-specific CD4+CD25+ regulatory T cells from human CD4+CD25- cells

Antigen-specificity is a hallmark of adaptive T cell-mediated immune responses. CD4+CD25+FOXP3+ regulatory T cells (T(R)) also require activation through the T cell receptor for function. Although these cells require antigen-specific activation, they are generally able to suppress bystander T cell responses once activated. This raises the possibility that antigen-specific T(R) may be useful therapeutically by localizing generalized suppressive activity to tissues expressing select target antigens. Here, we demonstrate that T(R) specific for particular peptide-MHC complexes can be generated from human CD4+CD25- T cells in vitro and isolated by using HLA class II tetramers. Influenza hemagglutinin epitopes were used to generate hemagglutinin-specific T(R), which required cognate antigen for activation but which subsequently suppressed noncognate bystander T cell responses as well. These findings have implications for the generation of therapeutic regulatory T cells in disease, and also suggest an important mechanism by which T cells may be regulated at the site of inflammation.     

Intratumoral CD4+CD25+ regulatory T-cell-mediated suppression of infiltrating CD4+ T cells in B-cell non-Hodgkin lymphoma

Most non-Hodgkin lymphomas (NHLs) are of B-cell origin, but the tumor tissue can be variably infiltrated with T cells. In the present study, we have identified a subset of CD4(+)CD25(+) T cells with high levels of CTLA-4 and Foxp3 (intratumoral T(reg) cells) that are overrepresented in biopsy specimens of B-cell NHL (median of 17% in lymphoma biopsies, 12% in inflammatory tonsil, and 6% in tumor-free lymph nodes; P = .001). We found that these CD4(+)CD25(+) T cells suppressed the proliferation and cytokine (IFN-gamma and IL-4) production of infiltrating CD4(+)CD25(-) T cells in response to PHA stimulation. PD-1 was found to be constitutively and exclusively expressed on a subset of infiltrating CD4(+)CD25(-) T cells, and B7-H1 could be induced on intratumoral CD4(+)CD25(+) T cells in B-cell NHL. Anti-B7-H1 antibody or PD-1 fusion protein partly restored the proliferation of infiltrating CD4(+)CD25(-) T cells when cocultured with intratumoral T(reg) cells. Finally, we found that CCL22 secreted by lymphoma B cells is involved in the chemotaxis and migration of intratumoral T(reg) cells that express CCR4, but not CCR8. Taken together, our results suggest that T(reg) cells are highly represented in the area of B-cell NHL and that malignant B cells are involved in the recruitment of these cells into the area of lymphoma.     

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。     

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.     

CD4+ and CD56+ acute monoblastic leukemia.

We report here a patient with acute monoblastic leukemia whose leukemia cells had CD4 (T4) and CD56 (NKH-1) antigens, in addition to CD36 (OKM5) antigen. The leukemia cells did not have NK or ADCC activities. They showed no rearrangements of immunoglobulin heavy (IgH) chain and T cell receptor (TCR)-beta chain genes, indicating that the leukemia cells were nonlymphoid. The presence of this case suggests that leukemia cells could be originated from monocytes with NK-associated antigen without IgH or TCR rearrangements.     

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+Treg细胞与支气管哮喘

CD4+ CD25+ Treg细胞的主要作用表现为免疫无能性和免疫抑制性,是外周免疫耐受形成机制的主要组成部分.其主要作用机制为分泌抑制性细胞因子(IL-10和TGF-β)、表达细胞表面分子(CTLA-4、GITR等)及Foxp3等.支气管哮喘患者外周血CD4+ CD25+ Treg功能及数量存在异常,这可能是支气管哮...