CD95/CD95L信号分子介导的细胞凋亡和非凋亡研究进展

CD95/CD95L系统是诱导细胞凋亡的重要途径,在人体自身耐受机制、诱导活化细胞凋亡、控制免疫应答和参与免疫豁免中均起重要的作用。然而近年来新的研究发现CD95/CD95L不仅能够诱导细胞凋亡还可促发多重信号通路抑制细胞凋亡,其表     

CD95/CD95L信号分子介导的细胞凋亡和非凋亡研究进展1

CD95/CD95L系统是诱导细胞凋亡的重要途径,在人体自身耐受机制、诱导活化细胞凋亡、控制免疫应答和参与免疫豁免中均起重要的作用.然而近年来新的研究发现CD95/CD95L不仅能够诱导细胞凋亡还可促发多重信号通路抑制细胞凋亡,其表达异常与肿瘤以及某些自身免疫性疾病的发生、发展有着密切联系.     

CD95介导细胞凋亡机制的最新研究动态

ＣＤ９５介导细胞凋亡机制的最新研究动态刘志国樊代明李恩善＊（第四军医大学西京医院全军消化中心＊免疫学教研室，西安７１００３２）ＣＤ９５（Ｆａｓ／Ａｐｏ－Ｉ）为神经生长因子／肿瘤坏死因子（ＮＧＦ／ＴＮＦ）受体超家族成员，主要表达于活化Ｔ细胞表面，其配体...     

CD14介导凋亡细胞清除的研究进展

CD14是一种膜锚着糖蛋白,可作为内毒素的主要受体,激活巨噬细胞释放前炎症因子,引发炎性级联反应.另一方面,CD14作为巨噬细胞识别清除凋亡细胞的受体之一,介导凋亡细胞的非炎性清除.     

CD4-CD8-双阴性T细胞在B细胞介导免疫反应中的作用

最近研究表明调节T细胞在免疫反应中发挥重要作用。CD4-CD8-双阴性T细胞(double negative T cell,DNT细胞),1种较少的调节T细胞亚群,在移植、肿瘤及自身免疫过程中发挥抗原特异性免疫调节功能。目前,在人类及小鼠的研究中发现DNT细胞不仅能抑制细胞和体液免疫应答,而且可以输入体内作为一种体细胞治疗来实现诱导免疫耐受和预防疾病。在这篇综述中,我们主要关注DNT细胞的起源,分子表型及其在B细胞相关免疫反应中的作用机制,以期利用DNT细胞更好地治疗B细胞介导的免疫性疾病。     

抗CD95单克隆抗体诱导的活化T细胞凋亡时转录因子nur77的表达

以抗ＣＤ９５的特异性单克隆抗体（ＣＨ－１１）诱导人Ｔ细胞Ｊｕｒｋａｔ细胞系发生凋亡,Ｊｕｒｋａｔ细胞在发生凋亡过程中出现典型的ＤＮＡ梯形片段化,以荧光染料（ＰＩ）标记的流式细胞学技术对于发生凋亡的细胞进行定量测定,证实发生凋亡的细胞百分比在各个时间点上为６．１％－４３．５％之间。     

Toll样受体信号介导细胞凋亡的研究进展

细胞凋亡在病毒、细菌等感染的过程中和肿瘤等疾病的发生发展中起至关重要的作用。Toll样受体(TLR)存在于巨噬细胞、肿瘤细胞等细胞表面,能直接识别并结合病原微生物和宿主细胞表面的病原相关分子模式,然后通过髓样分化因子88/Fas相关死亡结构域/caspase-8、TIR结构域接头蛋白/蛋白激酶/干扰素调节因子和核因子κB路径等信号途径对巨噬细胞、肿瘤细胞等细胞的凋亡起调节作用。随着对TLR介导的细胞凋亡中Fas相关死亡结构域、TIR结构域接头蛋白等多种信号分子的深入研究,有助于了解它们在细胞凋亡中的作用,并为感染和肿瘤等疾病的分子靶向治疗提供新的目标。     

一氧化氮介导的细胞凋亡

一氧化氮能够介导细胞凋亡，其机制有如下三点：（１）影响细胞的能量代谢，损害其能量状态从而导致细胞死亡。（２）作为一种活泼的氧化剂，破坏细胞氧化抗氧化的平衡状态。（３）ＤＮＡ损伤及突变作用     

重症肌无力患者外周血CD5+B细胞和CD4-CD8-T细胞的变化

研究重症肌无力 (MG )患者外周血CD5 + B细胞和CD4 CD8 T细胞的变化 ,以探讨这两种细胞与MG的关系。采用流式细胞仪分析MG患者和对照组外周血中CD5 + B细胞和CD4 CD8 T细胞的频率 ,同时以ELISA方法检测这些患者的血清AchR、PsmR抗体水平。结果 :2 8例MG患者的CD5 + B细胞为 19 75 %± 10 8% ,高于对照组的 15 4 %± 9 6 7% (P <0 0 1) ;胸腺未切除MG患者的CD5 + B细胞为 2 2 31%± 7 4 7% ,显著高于对照组 (P <0 0 0 1) ;两种抗体阳性MG患者的CD5 + B细胞为 2 4 96 %± 13 1% ,显著高于对照组 (P <0 0 0 1) ;以上各组MG患者的CD4 CD8 T细胞与对照组均无显著区别 ;两种抗体阴性组的CD5 + B细胞和CD4 CD8 T细胞亦与对照组均无显著区别 ;两种抗体阴性组的CD5 + B细胞和CD4 CD8 T细胞亦与对照组无明显差异。本研究提示MG患者外周血的CD5 + B细胞频率增高 ,与胸腺切除与否以及突触前后膜抗体的阳性程度密切相关 ,而CD4 CD8 T细胞是否与MG有关还需进一步研究证实。     

c-Myc介导的细胞凋亡途径

细胞凋亡是细胞生物学行为中一复杂的主动过程,受细胞内外多种因子调控。本文阐述了c-Myc在细胞凋亡中与其它癌基因、抑癌基因bcl-2、p53等产物的相互作用,与蛋白酶类的关系以及与Fas/FasL凋亡途径的偶联。表明c-Myc不仅是促进细胞增殖的重要因子,也是介导细胞凋亡的重要成员。     

骨组织工程中的间质干细胞：成骨活性、免疫特性、促血管化及成骨效应

BACKGROUND: It is still a challenge to repair bone defects caused by trauma, infection, tumor and congenital diseases. Bone tissue engineering is a promising method for bone defect repair showing important guiding significance in the clinic. OBJECTIVE: To review the progress of proliferation, osteogenic activity, immunogenicity, proangiogensis and in vivo osteogenic effect of mesenchymal stem cells in bone tissue engineering. METHODS: The first author retrieved Wanfang and PubMed datebase for literatures published from 2008 to 2016, using the keywords of “mesenchymal stem cell, tissue engineering, osteogenesis, immune property, angiogenesis” in Chinese and English, respectively. Articles regarding mesenchymal stem cells, tissue engineering, osteogenesis, immune property and angiogenesis were included, and repetitive and dated studies were excluded. Totally 1 772 articles were retrieved initially, and in accordance with inclusion and exclusion criteria, 41 eligible articles were included for review analysis. RESULTS AND CONCLUSION: Bone marrow mesenchymal stem cells and adipose-derived mesenchymal stem cells are extensively applied in bone tissue engineering. Studies have shown that the osteogenic activity of bone marrow mesenchymal stem cells is higher than that of adipose-derived mesenchymal stem cells, but its immune regulation effect is weaker than that of adipose-derived mesenchymal stem cells. Mesenchymal stem cells hold remarkable immune regulation (immunosuppression and immune enhancement) and tissue repair capacity, which can eliminate inflammatory reactions at injured sites, promoting tissue repair. Adipose-derived mesenchymal stem cells cultured under hypoxia environment can secret more angiogenic cytokines generating more vascular structures. Furthermore, increasing proof have confirmed that porous nano-polylactic acid combined with nano-carbon biological material can significantly promote the proliferation and osteogenesis of bone marrow mesenchymal stem cells. Taking its tumorigenesis into consideration, mesenchymal stem cells should be prudently used in the clinic. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

胚胎成纤维细胞和Ⅳ型胶原黏附分选表皮干细胞的比较研究

目的比较以Ⅳ型胶原和胚胎成纤维细胞黏附分选表皮干细胞的效率，探索从皮肤中快速表皮干细胞分选的有效方法。方法使用DispaseⅡ和CollagenaseⅠ混合酶、胰酶分步消化皮肤得到的细胞悬液，实验组用胚胎成纤维细胞，对照组使用Ⅳ型胶原，分别作为黏附基质，在细胞培养板中对表皮干细胞进行黏附筛选，培养5d后统计各组表皮干细胞克隆形成数量，评价筛选效率。结果经抗β-整合素单抗和抗角蛋白K19单抗免疫细胞染色确证形成克隆的细胞是表皮干细胞，在两个细胞密度水平，实验组和对照组培养出的表皮干细胞克隆数量差异无统计学意义（P〉0．05）。结论使用成纤维细胞分选表皮干细胞与使用Ⅳ型胶原方法分选效率相当，成纤维细胞条件培养液对黏附效率没有影响，但能促进表皮干细胞生长。     

Augmentation of Natural Killer Cell and Antibody-Dependent Cellular Cytotoxicity in BALB/c Mice by Sulforaphane,a Naturally Occurring Isothiocyanate from Broccoli through Enhanced Production of Cytokines IL-2 and IFN-γ

Effect of sulforaphane on cell-mediated immune (CMI) response was studied in normal as well as Ehrlich ascites tumor-bearing BALB/c mice. Administration of sulforaphane significantly enhanced natural killer (NK) cell activity in both normal as well as tumor-bearing animals, and the activity was observed earlier than in tumor-bearing control animals. Antibody-dependent cellular cytotoxicity (ADCC) also was enhanced significantly in both normal as well as tumor-bearing animals after sulforaphane administration compared with untreated control tumor-bearing animals. An early antibody-dependent complement-mediated cytotoxicity (ACC) also was observed in sulforaphane-treated normal and tumor-bearing animals. Administration of sulforaphane significantly enhanced the production of Interleukin-2 and Interferon-γ in normal as well as tumor-bearing animals. In addition, sulforaphane significantly enhanced the proliferation of splenocytes, bone marrow cells, and thymocytes by stimulating the mitogenic potential of various mitogens such as concanavalin A, phytohaemagglutinin, poke weed mitogen, and lipopolysaccharide.     

Augmentation of natural killer cell and antibody-dependent cellular cytotoxicity in BALB/c mice by sulforaphane, a naturally occurring isothiocyanate from broccoli through enhanced production of cytokines IL-2 and IFN-gamma

Effect of sulforaphane on cell-mediated immune (CMI) response was studied in normal as well as Ehrlich ascites tumor-bearing BALB/c mice. Administration of sulforaphane significantly enhanced natural killer (NK) cell activity in both normal as well as tumor-bearing animals, and the activity was observed earlier than in tumor-bearing control animals. Antibody-dependent cellular cytotoxicity (ADCC) also was enhanced significantly in both normal as well as tumor-bearing animals after sulforaphane administration compared with untreated control tumor-bearing animals. An early antibody-dependent complement-mediated cytotoxicity (ACC) also was observed in sulforaphane-treated normal and tumor-bearing animals. Administration of sulforaphane significantly enhanced the production of Interleukin-2 and Interferon-γ in normal as well as tumor-bearing animals. In addition, sulforaphane significantly enhanced the proliferation of splenocytes, bone marrow cells, and thymocytes by stimulating the mitogenic potential of various mitogens such as concanavalin A, phytohaemagglutinin, poke weed mitogen, and lipopolysaccharide.     

人胚胎干细胞向内皮细胞的分化诱导

BACKGROUND:Human embryonic stem cells exhibit self-renewal and multi-differentiation potential, and can differentiate into endothelial cells under certain induction conditions. OBJECTIVE:To explore induced conditions of the human embryonic stem cells differentiating into endothelial cells and to investigate the effect of vascular endothelial growth factors on the endothelial differentiation of human embryonic stem cells. METHODS:After resuscitation, passage 40 human embryonic stem cell lines H9 were subjected to suspension culture to prepare embryos, and after 5-day culture, these cells were cultured in attachment medium to differentiate into embryoid bodies, followed by induction with 50 µg/L vascular endothelial growth factors. Passage 2 and 15 embryonic stem cells after induced differentiation were taken for Dil-Ac-LDL uptake test and immunohistochemical staining, respectively. RESULTS AND CONCLUSION:After 1-day culture, cord-like or polygonal monolayer cells around embryoid bodies showed bud-like and radial growth with a relative rapid speed merging into surrounding colonies; at 2-3 days, the number of suspension cells increased further, but the small-round cells in the center began to die; at 5 days, embryoid bodies started to passage, and aggregated cells exhibited typical paving stone-like appearance. Moreover, some human embryonic cells after induced differentiation could actively take up fluorescent labeled LDL, and red fluorescent particles appeared. Additionally, passage 15 embryonic stem cells after induced differentiation could express CD31 and FLK-1. These findings suggest that human embryonic stem cells induced by vascular endothelial growth factors can differentiate into endothelial cells.     

干细胞相关因子在大鼠卵巢颗粒细胞中的表达

背景：现有研究表明,人与大鼠卵巢优势卵泡中的颗粒细胞具有表达干细胞特性的现象。 目的：探讨干细胞相关因子在大鼠卵巢颗粒细胞中的表达。 方法：将大鼠卵巢组织制作石蜡切片后,使用免疫组化法检测CD34,CD133,ABCG2/Bcrp1,Pou5f1/Oct-4的表达。卵泡穿刺法获取颗粒细胞,并使用免疫组化法检测FSHR受体的表达以鉴定颗粒细胞的纯度。免疫组化法检测颗粒细胞CD44,C-Kit的表达情况,RT-PCR检测卵巢组织与颗粒细胞ABCG2/Bcrp1、Pou5f1/Oct-4、Nanog基因的表达情况。 结果与结论：免疫组化法石蜡切片显示部分卵巢颗粒细胞CD34,CD133,ABCG2/Bcrp1,Pou5f1/Oct-4阳性表达,而Pou5f1/Oct-4蛋白的表达在卵泡发育的周期中逐步增多,并在黄体化的时候显著增强,形成白体后则消失,因而具有周期性表达的特点。卵泡穿刺法提取的原代颗粒细胞FSHR受体鉴定阳性率在95%以上。体外培养的颗粒细胞以长梭形或菱形为主,部分细胞有聚集生长现象,且CD44,C-Kit阳性表达。RT-PCR检测结果显示,卵巢组织与体外培养的颗粒细胞均不表达Nanog,卵巢低表达Pou5f1/Oct-4,强烈表达ABCG2/Bcrp1,颗粒细胞微弱表达Pou5f1/Oct-4,而ABCG2/Bcrp1表达较强。以上结果显示大鼠卵巢中的部分颗粒细胞具有干细胞的特性。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

T cell signaling mechanisms that regulate HIV-1 infection

The ability of human immunodeficiency virus type-1 (HIV-1) to establish a persistent infection is critically dependent on the cellular signals that regulate HIV-1 replication within target cells. The balance between numerous host factors that either enhance or suppress viral infection determines the clinical outcome. Perturbation of the steady-state level of viral replication can significantly influence the course and the speed at which the infection develops into clinical disease. Activation signals delivered to T cells by cytokines and antigen-presenting cells (APC), are key modulators of viral replication. Our laboratory seeks to decipher how HIV-1 exploits T cell signaling mechanisms and host factors that regulate viral replication. Elucidation of the molecular mechanisms by which cellular signals regulate the HIV-1 life cycle within target cells will significantly advance our understanding of host-virus interactions.