共查询到19条相似文献，搜索用时 187 毫秒
1.
在正常生理和应激生物环境中,叉头转录因子3(FOXP3)是调节性T细胞发育和抑制功能的重要转录因子。试验利用生物信息学在线工具及软件对FOXP3蛋白的理化性质、蛋白晶体结构、翻译后修饰以及其相互作用蛋白等进行了研究。研究发现FOXP3蛋白复合物主要包含NFAT1 DNA结合域和与脱氧核糖核酸结合的FOXP3 FKH结构域,并且通过多种翻译后修饰影响FOXP3蛋白构象和与其互作蛋白的相互作用,最终改变FOXP3蛋白活性以调节Treg抑制特征。研究结果可为今后深入研究FOXP3如何调节Treg抑制的新方法和增强自身免疫性疾病免疫耐受的新疗法提供参考。 相似文献
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目的:研究系统性红斑狼疮(SLE)患者外周血CD 4 CD 25 调节性T细胞及Foxp3基因的表达水平,了解它们在SLE发病机制中的作用。方法:分别收集25例SLE患者(SLE组)及健康人(对照组)外周抗凝静脉血,分离纯化T淋巴细胞。PE标记抗CD 4单抗,F ITC标记的抗CD 25单抗,作双色流式细胞术,分析SLE患者外周血CD 4 CD 25 调节性T细胞百分率,RT-PCR检测T细胞Foxp3 mRNA表达。结果:SLE组外周血CD 4 T、CD 4 CD 25 T细胞百分率及T细胞Foxp3 mRNA水平均低于对照组(P<0.01),并且CD 4 CD 25 T细胞百分率与Foxp3mRNA水平呈依赖关系(P<0.01)。结论:SLE患者外周血存在细胞免疫功能失调,CD 4 CD 25 调节性T细胞数量减少和Foxp3mRNA表达下调可能与SLE的免疫学发病机制有关。 相似文献
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抗原浓度和DC数量对OT-I小鼠CD8+ T细胞分化与增殖的影响 总被引：1，自引：0，他引：1
【目的】探讨细胞毒性T细胞(CTL)表位肽SIINFEKL浓度和树突状细胞(DC)数量对CD8+T细胞活化和增殖的影响。【方法】用小鼠重组粒细胞集落刺激性生物因子(GM-CSF)和IL-4诱导骨髓细胞来源的DC增殖和分化,将所得成熟树突状细胞(maDC)和SIINFEKL抗原肽,与免疫磁珠法分离的OT-I小鼠CD8+T细胞共培养。用不同质量浓度的SIINFEKL(100,10,1,0.1,0.01和0.001 ng/mL)或不同数量的DC(DC/T比例分别为1/20和1/5)与CD8+T细胞共培养,刺激CD8+T细胞增殖分化。于共培养不同时间收集细胞,流式细胞术测定CD8+T细胞的数量、分裂速度、细胞表面活化分子的表达丰度,碘化丙叮(PI)染色测定细胞活力。【结果】在任一DC/T比例下,SIINFEKL浓度过低,均不能引起CD8+T细胞的充分增殖,而高于CD8+T细胞最佳增殖浓度的SIINFEKL则导致CD8+T细胞数量减少;在SIINFEKL质量浓度为0.001~0.1 ng/mL时,增加DC数量能促进CD8+T细胞的扩增;而SIINFEKL质量浓度为1~100 ng/mL时,提高DC数量反而导致CD8+T细胞数量减少;高浓度抗原和DC数量能有效诱导CD8+T细胞的活化和分裂增殖,但过量刺激会使细胞死亡,导致CD8+T细胞数量减少。【结论】CD8+T细胞的增殖受DC数量和抗原肽浓度的共同调节,要获得持久有效的CD8+T细胞免疫,必须保证CD8+T细胞得到足够的抗原信号,同时避免抗原信号过强导致的细胞活化后死亡。 相似文献
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5.
[目的]探讨猪圆环病毒2型感染的猪肠上皮细胞对CD4+T细胞分化关键分子mRNA的影响.[方法]利用免疫磁珠法分离猪外周血CD4+T细胞,与猪圆环病毒2型感染48 h的猪肠上皮细胞共培养,收集共培养后72 h的T细胞,荧光定量PCR检测CD4+T细胞分化关键分子变化.[结果]荧光定量PCR检测显示,细胞因子 IL-4、IL-17A、IFN-γ、TGF-β1 与转录因子 T-bet、GATA3、RORγt、Foxp3的 mRNA 水平均被显著下调,而IL-10的mRNA水平被显著上调.[结论]感染猪圆环病毒2型猪肠上皮细胞抑制CD4+T细胞分化关键分子mRNA水平,提示CD4+T细胞向Th1细胞、Th2细胞、Th17细胞、调节性T细胞分化被抑制,而IL-10的上调激活CD4+T细胞向高分泌IL-10的CD4+T细胞分化. 相似文献
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目的 了解B细胞活化因子(BAFF)及调节性T(Treg)细胞在免疫性血小板减少症(ITP)发病中的作用.方法 采集34例ITP及28例健康对照者外周血,用流式细胞术检测外周血Treg细胞数,ELISA检测血浆BAFF水平.结果 ITP患者外周血Treg细胞/CD4+细胞比值低于对照者[(1.55±1.13)％ vs (2.73±0.83)％,P＜0.01],而血浆BAFF水平高于对照者[(1 426.14±1 280.67) μg/L vs (644.29±307.97) μg/L,P＜0.01].结论 BAFF与Treg细胞可能存在相互作用,从而参与ITP发病. 相似文献
7.
鸡骨髓源树突状细胞体外诱导培养及鉴定 总被引：1，自引：0，他引：1
为建立鸡骨髓源树突状细胞(DC,dendritic cells)体外培养方法,用重组鸡粒细胞-巨噬细胞集落刺激因子(rGM-CSF)和重组鸡白细胞介素4(rIL-4)体外诱导鸡骨髓细胞分化为DC,然后通过形态观察、表型鉴定及功能分析来初步鉴定所培养的DC。试验结果表明:培养7 d后,光学显微镜下观察到细胞表面不规则,有显著的树突状突起,呈典型的DC形态,流式细胞仪测得细胞表面CD11c和MHCⅡ分子的表达量分别为69.3%和63.0%。经脂多糖或CpG-ODN刺激24 h后的DC,其表面成熟分子标志CD40和CD86上调表达,同时其刺激同种异体T细胞增殖的能力显著增强(P<0.01)。结论:本试验建立的方法能在体外制备出大量具有较高纯度的鸡骨髓源DC,并具有体内DC的生物学特征。 相似文献
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目的研究免疫功能在大鼠骨质疏松发病环节中的作用。方法 36只新生雌性SD大鼠随机等分为6组,A、B、C、D、E、F组分别用生理盐水、谷氨酸单钠(MSG)、MSG+低剂量胸腺肽、MSG+高剂量胸腺肽、MSG+低剂量环孢素、MSG+高剂量环孢素灌胃,每周1次,连续7周。测定CD3、CD4、CD8和NK细胞数和体外T淋巴细胞转化功能,并进行骨组织形态学观察。结果 B组CD3、CD4、CD8、CD4/CD8、NK细胞及T淋巴细胞转化能力明显低于A组(P<0.01)。与B组比较,C、D组CD3、CD4、CD4/CD8、NK细胞及T淋巴细胞转化能力明显升高(P<0.01),骨质疏松明显减轻;而E、F组CD3、CD4、CD4/CD8、NK细胞及T淋巴细胞转化能力明显降低(P<0.01),骨质疏松明显加重。结论免疫功能低下诱发骨质疏松,而增强免疫功能减轻骨质疏松。 相似文献
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《农业科学与技术》2016,(10)
[目的]建立猪外周血单核细胞来源的树突状细胞(MoDC)体外培养模型。[方法]从猪外周新鲜血液中分离外周血单核细胞(PBMC),通过贴壁法获得树突状细胞前体细胞,采用重组猪的集落共刺激因子(rp GM-SCF)和重组猪的白细胞介素4(rp IL-4)双因子诱导及脂多糖(LPS)刺激成熟法,收集不同时间段的细胞,利用扫描电子显微镜观察其形态,流式细胞分析仪检测表面分子表达率及其对FITC-dextran的吞噬能力,混合淋巴细胞反应检测细胞对同种异体T细胞的刺激能力。[结果]经体外诱导的DC具有典型的树突状形态;LPS刺激的DC表型分子CD1a、CD80、CD86、SLAII、CD172a与LPS未刺激的DC有明显增高,其吞噬能力有所下降,刺激同种异体T淋巴细胞的能力有所增强。[结论]该试验成功建立了猪MoDC的体外诱导培养方法,为进一步研究猪MoDC在机体免疫调节和抗病毒感染中的作用奠定了基础。 相似文献
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《江苏农业学报》2016,(3)
为建立猪外周血单核细胞来源的树突状细胞(Mo DC)体外培养模型,从猪外周新鲜血液中分离外周血单核细胞(PBMC),通过贴壁法获得树突状细胞前体细胞,采用重组猪的集落共刺激因子(rp GM-CSF)和白细胞介素4(rp IL-4)双因子诱导及脂多糖(LPS)刺激成熟法,收集不同时间段的细胞,利用扫描电子显微镜观察其形态,流式细胞分析仪检测表面分子表达率及其对FITC-dextran的吞噬能力,混合淋巴细胞反应检测细胞对同种异体T细胞的刺激能力。结果表明,经体外诱导的细胞具有典型的树突状形态;经脂多糖刺激的树突状细胞表型分子CD1a、CD80、CD86、SLAII、CD172a与未经刺激的树突状细胞有明显增高,其吞噬能力有所下降,刺激同种异体T淋巴细胞的能力增强。本研究成功建立了猪Mo DC的体外诱导培养方法,为进一步研究其在机体免疫调节和抗病毒感染中的作用奠定了基础。 相似文献
11.
CTLA-4 control over Foxp3+ regulatory T cell function 总被引：1，自引：0，他引：1
Wing K Onishi Y Prieto-Martin P Yamaguchi T Miyara M Fehervari Z Nomura T Sakaguchi S 《Science (New York, N.Y.)》2008,322(5899):271-275
Naturally occurring Foxp3+CD4+ regulatory T cells (Tregs) are essential for maintaining immunological self-tolerance and immune homeostasis. Here, we show that a specific deficiency of cytotoxic T lymphocyte antigen 4 (CTLA-4) in Tregs results in spontaneous development of systemic lymphoproliferation, fatal T cell-mediated autoimmune disease, and hyperproduction of immunoglobulin E in mice, and it also produces potent tumor immunity. Treg-specific CTLA-4 deficiency impairs in vivo and in vitro suppressive function of Tregs-in particular, Treg-mediated down-regulation of CD80 and CD86 expression on dendritic cells. Thus, natural Tregs may critically require CTLA-4 to suppress immune responses by affecting the potency of antigen-presenting cells to activate other T cells. 相似文献
12.
Munn DH Sharma MD Lee JR Jhaver KG Johnson TS Keskin DB Marshall B Chandler P Antonia SJ Burgess R Slingluff CL Mellor AL 《Science (New York, N.Y.)》2002,297(5588):1867-1870
Antigen-presenting cells (APCs) can induce tolerance or immunity. We describe a subset of human APCs that express indoleamine 2,3-dioxygenase (IDO) and inhibit T cell proliferation in vitro. IDO-positive APCs constituted a discrete subset identified by coexpression of the cell-surface markers CD123 and CCR6. In the dendritic cell (DC) lineage, IDO-mediated suppressor activity was present in fully mature as well as immature CD123+ DCs. IDO+ DCs could also be readily detected in vivo, which suggests that these cells may represent a regulatory subset of APCs in humans. 相似文献
13.
Toll-like receptors (TLRs) control activation of adaptive immune responses by antigen-presenting cells (APCs). However, initiation of adaptive immune responses is also controlled by regulatory T cells (TR cells), which act to prevent activation of autoreactive T cells. Here we describe a second mechanism of immune induction by TLRs, which is independent of effects on costimulation. Microbial induction of the Toll pathway blocked the suppressive effect of CD4+CD25+ TR cells, allowing activation of pathogen-specific adaptive immune responses. This block of suppressor activity was dependent in part on interleukin-6, which was induced by TLRs upon recognition of microbial products. 相似文献
14.
Peng G Guo Z Kiniwa Y Voo KS Peng W Fu T Wang DY Li Y Wang HY Wang RF 《Science (New York, N.Y.)》2005,309(5739):1380-1384
CD4+ regulatory T (Treg) cells have a profound ability to suppress host immune responses, yet little is understood about how these cells are regulated. We describe a mechanism linking Toll-like receptor (TLR) 8 signaling to the control of Treg cell function, in which synthetic and natural ligands for human TLR8 can reverse Treg cell function. This effect was independent of dendritic cells but required functional TLR8-MyD88-IRAK4 signaling in Treg cells. Adoptive transfer of TLR8 ligand-stimulated Treg cells into tumor-bearing mice enhanced anti-tumor immunity. These results suggest that TLR8 signaling could play a critical role in controlling immune responses to cancer and other diseases. 相似文献
15.
Much progress has been made in understanding how the immune system is regulated, with a great deal of recent interest in naturally occurring CD4+ regulatory T cells that actively engage in the maintenance of immunological self-tolerance and immune homeostasis. The challenge ahead for immunologists is the further elucidation of the molecular and cellular processes that govern the development and function of these cells. From this, exciting possibilities are emerging for the manipulation of regulatory T cell pathways in treating immunological diseases and suppressing or augmenting physiological immune responses. 相似文献
16.
Interleukin-2 (IL-2), which is a growth factor for T lymphocytes, can also sometimes be inhibitory. Thus, the proliferation of CD8+ T cells in vivo is increased after the injection of a monoclonal antibody that is specific for IL-2 (IL-2 mAb), perhaps reflecting the removal of IL-2-dependent CD4+ T regulatory cells (T regs). Instead, we show here that IL-2 mAb augments the proliferation of CD8+ cells in mice simply by increasing the biological activity of preexisting IL-2 through the formation of immune complexes. When coupled with recombinant IL-2, some IL-2/IL-2 mAb complexes cause massive (>100-fold) expansion of CD8+ cells in vivo, whereas others selectively stimulate CD4+ T regs. Thus, different cytokine-antibody complexes can be used to selectively boost or inhibit the immune response. 相似文献
17.
The immune response is initiated in organized lymphoid tissues where antigen-loaded dendritic cells (DCs) encounter antigen-specific T cells. DCs function as packets of information that must be decoded by the T cell before an appropriate immune response can be mounted. We discuss how the dynamics of DC-T cell encounter and the mechanism of T cell differentiation make the decoding of this information stochastic rather than determinate. This results in the generation of both terminally differentiated effector cells and intermediates that play distinctive roles in protection, immunoregulation, and immunological memory. 相似文献
18.
Mounting a protective immune response is critically dependent on the orchestrated movement of cells within lymphoid organs. We report here the visualization, using major histocompatability complex class I tetramers, of the CD8-positive (CD8) T cell response in the spleens of mice to Listeria monocytogenes infection. A multistage pathway was revealed that included initial activation at the borders of the B and T cell zones followed by cluster formation with antigenpresenting cells leading to CD8 T cell exit to the red pulp via bridging channels. Strikingly, many memory CD8 T cells localized to the B cell zones and, when challenged, underwent rapid migration to the T cell zones where proliferation occurred, followed by egress via bridging channels in parallel with the primary response. Thus, the ability to track endogenous immune responses has uncovered both distinct and overlapping mechanisms and anatomical locations driving primary and secondary immune responses. 相似文献
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为了观察马齿苋多糖(Portulace oleracea polysaccharide,POP)对雏鸡胸腺免疫功能的影响,并探讨其可能的作用机制,试验通过对雏鸡灌注不同剂量的POP,测定雏鸡胸腺指数,应用MMT(四甲基偶氮唑盐比色法)方法测定雏鸡胸腺淋巴细胞转化率,利用流式细胞器测定雏鸡胸腺淋巴细胞周期与胸腺T淋巴细胞亚群的变化.结果表明,POP能显著增加雏鸡胸腺淋巴细胞转化率和胸腺指数(P＜0.05),淋巴细胞增殖指数显著提高(P＜0.05),CD4+T淋巴细胞含量显著增加(P＜0.05),CD8+T淋巴细胞数量变化不明显,CD4+/CD8+T淋巴细胞比值显著升高(P＜0.05).POP可通过调节雏鸡胸腺内细胞水平的变化,增强雏鸡细胞免疫功能,促进免疫系统发育. 相似文献