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Self-activation of Vγ9Vδ2 T cells by exogenous phosphoantigens involves TCR and butyrophilins
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作者 ChloéLaplagne Laetitia Ligat +5 位作者 Juliet Foote Frederic Lopez Jean-Jacques Fournié Camille Laurent Salvatore Valitutti Mary Poupot 《Cellular & Molecular Immunology》 SCIE CAS CSCD 2021年第8期1861-1870,共10页
The high cytotoxic activity of Vγ9Vδ2 T lymphocytes against tumor cells makes them useful candidates in anticancer therapies.However,the molecular mechanism of their activation by phosphoantigens(PAgs)is not complet... The high cytotoxic activity of Vγ9Vδ2 T lymphocytes against tumor cells makes them useful candidates in anticancer therapies.However,the molecular mechanism of their activation by phosphoantigens(PAgs)is not completely known.Many studies have depicted the mechanism of Vγ9Vδ2 T-cell activation by PAg-sensed accessory cells,such as immune presenting cells or tumor cells.In this study,we demonstrated that pure resting Vγ9Vδ2 T lymphocytes can self-activate through exogenous PAgs,involving their TCR and the butyrophilins BTN3A1 and BTN2A1.This is the first time that these three molecules,concurrently expressed at the plasma membrane of Vγ9Vδ2 T cells,have been shown to be involved together on the same and unique T cell during PAg activation.Moreover,the use of probucol to stimulate the inhibition of this self-activation prompted us to propose that ABCA-1 could be implicated in the transfer of exogenous PAgs inside Vγ9Vδ2 T cells before activating them through membrane clusters formed byγ9TCR,BTN3A1 and BTN2A1.The self-activation of Vγ9Vδ2 T cells,which leads to self-killing,can therefore participate in the failure ofγδT cell-based therapies with exogenous PAgs and should be taken into account. 展开更多
关键词 Vγ9Vδ2 T cells phosphoantigen Butyrophilins T-cell receptor
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嗜乳脂蛋白3A1(BTN3A1)促进结核杆菌耐热抗原诱导的人外周血Vγ9Vδ2 T细胞活化增殖 被引量:1
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作者 唐洁 孙静 +6 位作者 查成 常见荣 胡坤 方强 陈雨晴 陈静 李柏青 《细胞与分子免疫学杂志》 CAS CSCD 北大核心 2020年第8期680-686,共7页
目的初步探讨嗜乳脂蛋白3A1(BTN3A1)在结核杆菌耐热抗原(MTB-HAg)诱导的人外周血Vγ9Vδ2 T细胞活化增殖中的作用。方法人外周血单个核细胞(PBMC)先加BTN3A1阻断性抗体作用3 h,再分别用MTB-HAg和磷酸类抗原(PAg)刺激培养24 h后收集细胞... 目的初步探讨嗜乳脂蛋白3A1(BTN3A1)在结核杆菌耐热抗原(MTB-HAg)诱导的人外周血Vγ9Vδ2 T细胞活化增殖中的作用。方法人外周血单个核细胞(PBMC)先加BTN3A1阻断性抗体作用3 h,再分别用MTB-HAg和磷酸类抗原(PAg)刺激培养24 h后收集细胞,用流式细胞术检测Vγ9Vδ2 T细胞中CD69表达;或刺激20 h后收集细胞,检测Vγ9Vδ2 T细胞中1型辅助性T(Th1)细胞因子γ干扰素(IFN-γ)和肿瘤坏死因子α(TNF-α)产生细胞比例;或刺激后,在含白细胞介素2(IL-2)培养液中培养10 d后,收集细胞检测Vγ9Vδ2 T细胞扩增比例及增殖活性。结果MTB-HAg刺激后,Vγ9Vδ2 T细胞中CD69平均荧光强度和阳性细胞比例在BTN3A1阻断组均明显下降(为刺激组的13.84%和43.00%);而PAg阻断组的CD69平均荧光强度和阳性细胞比例显著被抑制(为刺激组的3.10%,4.47%和9.53%,10.91%)。MTB-HAg刺激后Vγ9Vδ2 T细胞中IFN-γ和TNF-α产生细胞比例在BTN3A1阻断组显著减少,Vγ9Vδ2 T细胞扩增数量和细胞增殖活性在BTN3A1阻断组也显著减少或降低。与PAg阻断组明显被抑制的结果相似。结论BTN3A1促进MTB-HAg诱导的外周血Vγ9Vδ2 T细胞活化增殖。 展开更多
关键词 嗜乳脂蛋白3A1(BTN3A1) 结核杆菌耐热抗原(MTB-HAg) 磷酸类抗原(PAg) Vγ9Vδ2 T细胞
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结核杆菌耐热抗原和磷酸类抗原对人外周血γδ T细胞活化和增殖的比较 被引量:7
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作者 丁艳 盛玲玲 +2 位作者 邱晓静 徐丹 李柏青 《蚌埠医学院学报》 CAS 2012年第7期745-747,共3页
目的:比较结核杆菌耐热抗原(Mtb-HAg)和磷酸类抗原(HDMAPP)刺激正常人外周血γδT细胞活化和增殖的特点。方法:健康成人外周血单个核细胞(PBMC,1×106/ml),分别加Mtb-HAg(5μg/ml)和HDMAPP(2×10-9mol/ml)进行刺激,同时给予IL-2... 目的:比较结核杆菌耐热抗原(Mtb-HAg)和磷酸类抗原(HDMAPP)刺激正常人外周血γδT细胞活化和增殖的特点。方法:健康成人外周血单个核细胞(PBMC,1×106/ml),分别加Mtb-HAg(5μg/ml)和HDMAPP(2×10-9mol/ml)进行刺激,同时给予IL-2(50 u/ml)维持细胞增殖,另外设立只加IL-2的对照组。培养10 d后,采用抗CD3-FITC和抗TCRγδ-PE荧光抗体标记细胞,流式细胞术检测γδT细胞的比例。结果:正常人PBMC经Mtb-HAg刺激扩增后γδT细胞在扩增细胞中的比例明显低于HDMAPP组(P<0.01),均明显高于IL-2对照组(P<0.01)。各个体对2种抗原刺激扩增γδT细胞呈线性正相关关系(R2=0.855 1,P<0.01)。结论:Mtb-HAg和HDMAPP均可优势激活人γδT细胞,且后者较前者有更强的活性。 展开更多
关键词 结核杆菌耐热抗原 磷酸类抗原 ΓΔT细胞
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The promise of γδ T cells and the γδ T cell receptor for cancer immunotherapy 被引量:10
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作者 Mateusz Legut David K Cole Andrew K Sewell 《Cellular & Molecular Immunology》 SCIE CAS CSCD 2015年第6期656-668,共13页
γδ T cells form an important part of adaptive immune responses against infections and malignant transformation. The molecular targets of humanγδT cell receptors (TCRs) remain largely unknown, but recent studies ... γδ T cells form an important part of adaptive immune responses against infections and malignant transformation. The molecular targets of humanγδT cell receptors (TCRs) remain largely unknown, but recent studies have confirmed the recognition of phosphorylated prenyl metabolites, lipids in complex with CD1 molecules and markers of cellular stress. All of these molecules are upregulated on various cancer types, highlighting the potential importance of the γδ T cell compartment in cancer immunosurveiliance and paving the way for the use of γδTCRs in cancer therapy. Ligand recognition by the γδ TCR often requires accessorylco-stimulatory stress molecules on both T cells and target cells; this cellular stress context therefore provides a failsafe against harmful self-reactivity. Unlike αβ T cells, γδ T cells recognise their targets irrespective of HLA haplotype and therefore offer exciting possibilities for off-the-shelf, pan-population cancer immunotherapies. Here, we present a review of known ligands of human γδ T cells and discuss the promise of harnessing these cells for cancer treatment. 展开更多
关键词 CANCER γδ T cells IMMUNOTHERAPY phosphoantigens T cell receptor
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Vlultifunctional immune responses of HMBPP-specific Jy2Vδ2 T cells in M. tuberculosis and other infections 被引量:11
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作者 Zheng W Chen 《Cellular & Molecular Immunology》 SCIE CAS CSCD 2013年第1期58-64,共7页
Vy2Vδ2 T (also known as Vy9Vδ2 T) cells exist only in primates, and in humans represent a major yδ T-cell sub-population in the total population of circulating yδ T cells. Results from recent studies suggest tha... Vy2Vδ2 T (also known as Vy9Vδ2 T) cells exist only in primates, and in humans represent a major yδ T-cell sub-population in the total population of circulating yδ T cells. Results from recent studies suggest that while (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) phosphoantigen from Mycobacterium tuberculosis (Mtb) and other microbes activates and expands primate Vy2Vδ2 T cells, the Vy2Vδ2 T-cell receptor (TCR) recognizes and binds to HMBPP on antigen-presenting cells (APC). In response to HMBPP stimulus, Vy2V82 TCRs array to form signaling-related nanoclusters or nanodomains during the activation of Vy2V82 T cells. Primary infections with H MBPP-producing pathogens drive the evolution of multieffector functional responses in Vy2Vδ2 T cells, although Vy2V82 T cells display different patterns of responses during the acute and chronic phases of Mtb infection and in other infections. Expanded Vy2Vδ2 T cells in primary Mtb infection can exhibit a broader TCR repertoire and a greater clonal response than previously assumed, with different distribution patterns of Vδ,2Vδ2 T-cell clones in lymphoid and non-lymphoid compartments. Emerging in vivo data suggest that HMBPP activation of Vy2W2 T cells appears to impact other immune cells during infection. 展开更多
关键词 (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate T cell HMBPP human infection phosphoantigen T cell receptor T-cell response TUBERCULOSIS
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