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慢性HBV感染者调节性T细胞、黏附细胞对细胞毒T淋巴细胞体外增殖的影响
乙型肝炎患者体内细胞毒T淋巴细胞(cytotoxic T lymphocytes,CTL)的功能和数量直接影响着病毒的清除和肝细胞的损伤.本实验主要探讨慢性HBV感染者调节性T细胞(Tr)、黏附细胞(AC)对HLA-A2限制的HBV特异性CTL体外增殖的影响.
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阻断病毒抗原提呈途径在免疫逃逸机制中的研究
抗原的加工和提呈在适应免疫应答过程中发挥着中枢作用,是淋巴细胞活化、增生、发挥效应的始动环节,也是启动特异性免疫的关键步骤。病毒抗原肽提呈的过程包括病毒蛋白经胞质中的蛋白酶体降解成抗原多肽,由抗原加工相关转运子( transporter associated with antigen presentation, TAP)转运至内质网( endoplasmic reticulum,ER)腔内,与糖基修饰的主要组织相容性复合体( major histocompatibility complex,MHC)分子共同组成MHC-抗原肽分子复合体,经高尔基复合体(Golgi complex,GC)提呈至细胞表面,被T细胞受体(T cell receptor,TCR)识别,激活特异性细胞毒性T淋巴细胞(cytotoxic T lymphocytes,CTL)等一系列反应。
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LIGHT 一个新的非CD28依赖的T细胞共刺激分子
LIGHT(for homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes)〔1〕是1998年发现的TNF超家族成员,又称为HVEM-L (herpesvirus entry mediator-ligand)〔2〕是肿瘤坏死因子超家族的第14个成员(TNFSF14)。由于LIGHT同时具有诱导肿瘤细胞凋亡和共刺激T细胞活化的功能,它有希望为肿瘤的治疗带来新的方法。
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自然杀伤细胞表面受体NKp46的研究进展
一、自然杀伤细胞(natural killer cells,NK细胞)简介NK细胞来源于骨髓的淋巴细胞,是机体抵抗病毒感染和防止肿瘤发生的第一道防线,与T细胞不同,NK细胞无需抗原的刺激即可杀伤靶细胞.NK细胞表面活化性受体和抑制性受体的平衡调控NK细胞的活性[1].NK细胞表面受体包含在免疫球蛋白超家族(immunogloblin gene superfamily,IgSF)或细胞毒性T淋巴细胞受体(cytotoxic T lymphocytes receptor,CTLR)两个超家族中.NK细胞表面的活化受体分为人类白细胞抗原I(human leukocyte antigen-I,HLA-I)类分子相关受体和非相关受体,前者包括杀伤细胞免疫球蛋白样受体二区域(killer cell immunoglobulin-like receptor,2 do-mains short,KIB2DS),杀伤细胞免疫球蛋白样受体三区域(killer cell immunoglobulin-like receptor,3 domains short,KIR3DS)及NK细胞受体2C(natural killer cell group 2C,CD94/NKG2C);后者主要有NK细胞受体2区域(natural kil-ler cell group 2D,NKG2D)和自然细胞毒性受体(natural cytotoxicity receptors,NCR;包括Nkp46、Nkp30、Nkp44)及DNAX辅助分子1(DNAX accessory molecule-1,DNAM-1)[2];而相应的抑制性受体为KIR2DL、KIR3DL及CD94/NKG2A等.
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肺癌组织中树突状细胞浸润的意义
目前已经清楚,由树突状细胞(dendritic cells,DCs)等抗原递呈细胞(antigen presenting cells,APCs)所激活的T细胞介导的细胞毒性T淋巴细胞(cytotoxic T lymphocytes, CTLs)反应,在机体抗肿瘤中起着主导作用[1].诸多研究表明,DCs作为体内功能强的一类专职APCs,与肿瘤的发生、发展及预后有着密切的关系.为此,我们观察了肺癌组织中DCs的浸润情况并探讨其在临床上的应用价值.
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IL- 7和IL- 15自杀式基因修饰的中枢性记忆T细胞具有同种异基因反应性及自我更新的能力
白血病经同种异基因造血干细胞移植治疗后,其长期的临床缓解还依赖于同种异基因反应性记忆T细胞能否自我更新并分化成具有抗白血病作用的效应子,以对抗移植物抗宿主病(GVHD).记忆T细胞根据归巢受体CD62L和趋化因子受体CCR7的表达与否, 分为中枢性(TCM)和效应性(TEM)记忆T细胞.
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尘肺患者外周血T淋巴细胞亚群的改变
观察尘肺患者免疫功能的改变,探讨免疫反应在尘肺发病机制中的作用,我们对65例尘肺患者的外周血T淋巴细胞亚群做了检测和分析,现报告如下.
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人骨髓间充质干细胞对异体T淋巴细胞增殖及Treg细胞亚群的影响
间充质干细胞(MSC)可抑制移植物抗宿主病(GVHD),提高异基因移植的成功率[1],但具体机制尚不清楚.我们通过观察人MSC直接和间接对T淋巴细胞增殖及调节性T淋巴细胞(Treg)亚群的影响,探讨MSC抑制GVHD可能的作用机制.
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MAGE-1、-2、-3基因在消化道肿瘤中的表达
MAGEs(melanoma antigen genes)家族位于X染色体上,由17个基因成员组成的基因家族。 除了睾丸和胎盘外,它们在正常组织中均不表达。但在黑色素瘤、肺癌、乳腺癌、大肠癌等 恶性肿瘤中表达。它们编码的抗原肽可与人类白细胞抗原HLA(Human leukecyte Antigen )分子结合,形成抗原复合物, 与CTL受体结合, 被特异性CTLs(cytolytic T lymphocytes )细胞所识别,激活特异性CTL的杀伤活力。因此MAGEs基因编码蛋白成为肿瘤免疫治疗的靶 抗原。本文采用RT-PCR检测MAGE-1、2、3在消化道肿瘤患者的分布,以分析其在消化道肿 瘤中免 疫治疗的应用价值。
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Th17细胞、IL-17A mRNA及IL-23R mRNA与寻常性银屑病的关系
目的 探讨寻常性银屑病(PV)皮损中IL-17A mRNA及IL-23R mRNA水平、外周血CD4+IL-17+T细胞数量及它们与疾病严重程度的关系.方法 PV组25例,对照组14例.对PV皮损面积和严重指数( PASI)评分,用RT-PCR检测皮肤中IL-17A mRNA及IL-23R mRNA的水平,并用流式细胞仪测定20例PV患者及10例对照组外周血CD4+IL-17+T细胞的数量.结果 PV组IL-17A mRNA的水平明显高于对照组(0.996±0.231比0.437±0.096,t=10.57,P< 0.05),IL-23R mRNA水平也明显高于对照组(1.006±0.339比0.491±0.196,t=6.02,P<0.05).PV皮损中IL-17A mRNA与IL-23R mRNA的水平与PASI均呈线性正相关(分别为rs=0.67,P<0.05;rs=0.70,P<0.05).外周血CD4+IL-17+T细胞数量在两组差异无统计学意义.PV组中,外周血中CD4+IL-17+T细胞数量与皮损中IL-17A mRNA、IL-23RmRNA水平无相关性.结论 PV皮损中IL-17A mRNA及IL-23R mRNA的水平升高,与疾病严重程度相关,外周血Th17细胞数量无改变.
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GM-CSF诱导人脐血CD34+造血干细胞CXC细胞趋化因子受体-3表达和配体Γip-10、Mig功能研究
CXCR3, know to be predominately expressed on memory/activated T lymphocytes,is a receptor for both γ IP-10 and Mig. We report a novel finding that CXCR3 is also expressed on GM-CSF-stimulated, but not freshly isolated, CD34+ hematopoietic progenitors from human cord blood. Freshly isolated CD34 + progenitors express low level CXCR3 mRNA, but this expression is highly up-regulated by GM-CSF detected using real time quantitative RT-PCR technique. γ IP-10 and Mig induced GM-CSF stimulated CD34+ progenitor chemotaxis via CXCR3 documented by the fact that anti-CXCR3 mAb blocks γ IP-10 and Mig-induced CD34+ progenitor chemotaxis. These chemotactic attracted CD34+ progenitors are colonyforming unit-ganulocyte macrophages. Besides induction to chemotaxis, γIP-10 and Mig also induce GM-CSF-stimulated CD34+ progenitor adhesion and aggregation via CXCR3,confirmed by the observation that anti-CXCR3 mAb blocks these functions of γIP-10 and Mig,but not of SDF-1α.γ IP-10 and Mig-induced integrin (CD49a and CD49b) up-regulation plays crucial role in adhesion of GM-CSF-stimulated CD34+ progenitors. Moreover,γ IP-10 and Mig stimulated CXCR3 redistribution and cellular polarization in GM-CSF-stimulated CD34+ progenitors. These results indicate that CXCR3-γ IP-10 and -Mig receptor-ligand pairs as well as the effects of GM-CSF on them may be especially important in cytokine/chemokine environment for the physiological and pathophysiological events of differentiation of CD34+ hematopoietic progenitors into lymphoid and myeloid stem cells, subsequently immune/infl mmatory cells. These processes are including transmigration, relocation,differentiation and maturation of CD34+ hematopoietic progenitors.
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调节性T淋巴细胞在移植免疫耐受领域的临床应用研究
CD4~+ CD25~+ Foxp3~+ 调节性T淋巴细胞(Treg)是一类具有免疫调节功能的T淋巴细胞亚群,其免疫抑制功能成为近年来免疫学领域研究的重要内容~([1]).Treg不仅在维持机体免疫自稳方面发挥关键的作用,而且在移植后诱导和维持免疫耐受方面的作用也越来越受到人们的重视~([2]).
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EpCAM特异性免疫效应细胞对EpCAMhigh腺癌细胞的体外杀伤实验研究
背景:上皮细胞粘附分子(EpCAM CD326)高表达于多种实体腺癌细胞表面,包括结肠癌、胃癌、乳腺癌等。EpCAM在胃肠道肿瘤细胞>95%,与肿瘤细胞的增殖及肿瘤预后有密切关系。近年来, EpCAM已经成为肿瘤免疫治疗的一个新靶点,培养EpCAM特异性免疫效应细胞(Ep-effector)制备新高效特异性杀伤细胞。目的:探讨体外制备的EpCAM抗原特异性免疫效应细胞的特异性杀伤功能。并比较其与腺癌细胞裂解物特异性免疫效应细胞、CIK细胞杀伤功能的差异。方法:采集健康成人外周血,分离淋巴细胞及imDCs。体外诱导淋巴细胞中T细胞转化为CIK细胞并扩增。本实验首次以纯化EpCAM多肽抗原负载imDCs生成EpCAM-mDCs(Ep-mDCs),Ep-mDCs与自体CIK细胞体外共培养,制备成纯化EpCAM抗原特异性DC-CIK-CTL效应细胞(Ep-effector)。相似的方法,制备LS174-T腺癌细胞全抗原特异性DC-CIK-CTL效应细胞(LS-effector)。设单纯CIK组、LS-effector组及Ep-effector组,选择EpCAMhighLS174-T结肠腺癌细胞及EpCAMlowPaCa-2胰腺癌细胞作为靶细胞。细胞毒试验(CCK-8法)检测不同效靶比时各组效应细胞对EpCAMhigh的LS174-T及EpCAMlow的PaCa-2的杀伤效率。结果:体外制备LS-mDCs及Ep-mDCs表面分子表达量无差异(P>0.05)。随效靶比(E∶T)增高,各组效应细胞对LS174-T及PaCa-2的杀伤效率均升高。Ep-effector组对LS174-T的杀伤效率高于LS-effector组及单纯CIK组,LS-effector组与单纯CIK组无统计学差异;对PaCa-2的杀伤效率,两两组间比较无统计学差异(P>0.05)。结论:本实验首次应用EpCAM负载人外周血来源DC细胞制备Ep-mDCs,并证实其拥有激活T细胞生成特异性CTL的功能,由其制备的效应细胞(Ep-effector)对EpCAMhigh腺癌细胞具有更高的特异性杀伤活性。
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恶性黑色素瘤抗原基因与胃肠肿瘤
人类恶性黑色素瘤细胞携带有可以被特异性的细胞毒 T淋巴细胞( cytoxic T lymphocytes, CTL)所识别的抗原.恶性黑色素瘤抗原基因( melanoma antigens gene, MAGE)家族包含 17个成员,除睾丸和胎盘外,几乎仅限于肿瘤组织中表达.与 MAGE-1基因一样, MAGE-3基因编码的肿瘤抗原亦将人类白细胞抗原( HLA)-A1作为存在的前提 [1].此基因在黑色素瘤中的表达率高于 MAGE-1,并且可以于多种组织来源肿瘤中表达.由 MAGE编码的抗原具有严格的肿瘤特异性, MAGE基因在消化道肿瘤特异性和广泛表达使得 MAGE肽疫苗治疗消化道肿瘤成为可能.
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Objective:To study the vitamin D3 levels in primary Sjogren's syndrome patients and its correlation with severity and immune function.Methods:Active pSS patients, stable pSS patients and healthy volunteers were chosen for study. Peripheral blood was collected, mononuclear cells were isolated and percentages of CD27high plasma cells and CD27+ memory B cells were detected; serum was collected and contents of 1,25(OH)2D3, TNF-α, IL-6, IL-10 and IL-17 were detected.Results:(1) 1,25(OH)2D3 contents in serum as well as CD27high plasma cell and CD27+ memory B cell contents in peripheral blood of pSS group were lower than those of control group; serum TNF-α, IL-6 and IL-17 contents were higher than those of control group and IL-10 contents were lower than those of control group; (2) 1,25(OH)2D3 contents in serum as well as CD27high plasma cell and CD27+ memory B cell contents in peripheral blood of active pSS patients were lower than those of stable pSS patients; serum TNF-α, IL-6 and IL-17 contents were higher than those of stable pSS patients and IL-10 contents were lower than those of stable pSS patients; (3) 1,25(OH)2D3 level was positively correlated with contents of CD27highplasma cells, CD27+ memory B cells and IL-10, and negatively correlated with TNF-α, IL-6 and IL-17 contents.Conclusion:Abnormal reduction of Vitamin D3 levels is involved in the pathogenesis of primary Sjogren's syndrome and closely related to the severity and immune function of the disease.