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tim-3及其配体Galectin-9与病毒感染的关系

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基础医学与临床 2012年第9期32卷 1095-1098页

作者：赵慧王亮马秀敏丁剑冰新疆医科大学第一附属医院省部共建国家重点实验室培育基地新疆重大疾病医学重点实验室新疆乌鲁木齐830011 新疆医科大学第一附属医院检验科新疆乌鲁木齐830011 新疆医科大学基础医学院新疆乌鲁木齐830011

T细胞免疫球蛋白黏蛋白3(tim-3)基因是tim家族成员,与其配体半乳凝素-9(Galectin-9)结合可显著抑制T细胞的活化和增殖,并调节细胞因子的表达和分泌。tim-3/Galectin-9参与免疫反应的调节及抗病毒免疫反应,阻断此通路可促进CD8+T细胞应... 详细信息

T细胞免疫球蛋白黏蛋白3(tim-3)基因是tim家族成员,与其配体半乳凝素-9(Galectin-9)结合可显著抑制T细胞的活化和增殖,并调节细胞因子的表达和分泌。tim-3/Galectin-9参与免疫反应的调节及抗病毒免疫反应,阻断此通路可促进CD8+T细胞应答和对病毒的控制。因此,tim-3/Galectin-9通路可能与病毒感染慢性化有关。本文对tim-3及其配体的生物学特性、功能及在病毒感染中的研究近况进行综述。

关键词： tim-3 Galectin-9 病毒感染

tim-3在慢性HBV感染中的免疫调节作用

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中国免疫学杂志 2016年第2期32卷 267-270,274页

作者：余真君朱坚胜温州医科大学附属台州医院感染科临海317000

慢性乙型肝炎病毒（Hepatitis B virus,HBV）感染是世界范围内最常见的慢性病毒性感染,全球约有20亿人口有血清学证据证实现症或既往感染HBV,其中约3.5亿人口罹患慢性HBV感染[1,2];慢性HBV感染可致慢性肝病,与肝硬化、肝癌的发生密切相... 详细信息

慢性乙型肝炎病毒（Hepatitis B virus,HBV）感染是世界范围内最常见的慢性病毒性感染,全球约有20亿人口有血清学证据证实现症或既往感染HBV,其中约3.5亿人口罹患慢性HBV感染[1,2];慢性HBV感染可致慢性肝病,与肝硬化、肝癌的发生密切相关,在2010年全球疾病负担研究中,HBV感染位居首位,在导致死亡的病因中位列第10（78.6万/年）[3],基于这些数据,

关键词：免疫调节作用 tim-3 细胞内免疫全球疾病负担慢性肝病病毒性感染既往感染免疫功能障碍免疫反应信号通路

tim-3在口腔鳞癌患者外周血NK细胞的表达及意义

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实用口腔医学杂志 2016年第5期32卷 692-695页

作者：顾小军王腾勇刘新庆徐速章根训刘瑞英新余市人民医院口腔科 338000 新余市人民医院检验科 338000 江西省人民医院口腔科

目的:探讨T细胞免疫球蛋白粘蛋白分子-3(tim-3)在口腔鳞癌患者外周血自然杀伤细胞(NK细胞)上的表达及其临床意义。方法:应用流式细胞仪检测72例口腔鳞癌患者和40例健康对照者外周血CD3^-CD56^+NK细胞表面tim-3表达水平,分析其与口腔鳞... 详细信息

目的:探讨T细胞免疫球蛋白粘蛋白分子-3(tim-3)在口腔鳞癌患者外周血自然杀伤细胞(NK细胞)上的表达及其临床意义。方法:应用流式细胞仪检测72例口腔鳞癌患者和40例健康对照者外周血CD3^-CD56^+NK细胞表面tim-3表达水平,分析其与口腔鳞癌患者临床病理特征的关系。结果:口腔鳞癌患者外周血NK细胞的百分率为(9.30±2.52)%,显著低于健康对照组(17.36±3.15)%(Ptim-3的百分率为(14.35±6.35)%,显著高于健康对照组(1.78±0.86)%(Ptim-3在口腔鳞癌NK细胞的表达上调可能与口腔鳞癌的发生发展有关。

关键词：口腔鳞癌 NK细胞 tim-3

tim-3在小鼠心脏移植受者体内不同部位T淋巴细胞上表达的变化

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中华器官移植杂志 2010年第3期31卷 141-143页

作者：方泽民何文涛王升蔡兰军雒真龙张维娜周鸿敏陈忠华明长生华中科技大学同济医学院附属同济医院器官移植研究所教育部/卫生部器官移植重点实验室武汉430030

目的检测激活的TH1类淋巴细胞标记分子“T淋巴细胞免疫球蛋白域及粘蛋白域蛋白-3（tim-3）”在受者体内不同部位T淋巴细胞上表达的变化，探讨其与急性排斥反应的关系。方法建立小鼠同基因和异基因心脏移植模型（简称：同基因组和异基... 详细信息

目的检测激活的TH1类淋巴细胞标记分子“T淋巴细胞免疫球蛋白域及粘蛋白域蛋白-3（tim-3）”在受者体内不同部位T淋巴细胞上表达的变化，探讨其与急性排斥反应的关系。方法建立小鼠同基因和异基因心脏移植模型（简称：同基因组和异基因组）；移植术后第3和第6天，分离和制备两组受者外周血、脾脏、引流淋巴结和移植心内淋巴细胞悬液，采用流式细胞仪检测tim-3阳性细胞在CD4＋和CD8＋T淋巴细胞中的比值。结果两组受者术后外周血和脾脏内tim-3＋／CD4＋以及tim-3＋／CD8＋的比值比较，差异均无统计学意义（P〉0．05）。与同基因组比较，异基因组引流淋巴结内tim-3＋／CD4＋比值轻度升高（P〈0．05）；但异基因组术后第6天与第3天比较，差异无统计学意义（P〉0．05）。与同基因组比较，移植心内tim-3＋／CD4＋和tim-3＋／CD8＋比值均显著升高（P〈0．01）；异基因组术后第6天与第3天比较，移植心内tim-3＋／CD4＋和tim-3＋／CD8＋比值也显著升高（P＜0．01）。结论小鼠异基因心脏移植受者引流淋巴结和移植心内T淋巴细胞上tim-3的表达升高与急性排斥反应的进展动态相关。

关键词： tim-3 心脏移植移植物排斥 T淋巴细胞

tim-3基因多态性与儿童咳嗽变异性哮喘的关系

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第三军医大学学报 2012年第22期34卷 2302-2305页

作者：吴立强陈建平何念海桂芹晏玲陈盛第三军医大学西南医院儿科重庆400038

目的探讨重庆地区汉族人群中哮喘免疫调节基因tim-3启动子区3个单核苷酸多态性(SNP)位点与儿童咳嗽变异性哮喘(CVA)易感性的关联性。方法选取本科就诊CVA儿童200例,平均年龄6.8岁,作为CVA组,对照组儿童215例平均年龄6.9岁;采用(PCR-RFLP... 详细信息

目的探讨重庆地区汉族人群中哮喘免疫调节基因tim-3启动子区3个单核苷酸多态性(SNP)位点与儿童咳嗽变异性哮喘(CVA)易感性的关联性。方法选取本科就诊CVA儿童200例,平均年龄6.8岁,作为CVA组,对照组儿童215例平均年龄6.9岁;采用(PCR-RFLP)聚合酶链反应-限制性片段长度多态性检测所有研究对象tim-3基因启动子区Rs1051746、Rs4704853、Rs10053538三个多态性位点基因多态性,进行病例对照研究分析。结果 PCR-RFLP检测结果显示,Rs1051746位点单核苷酸多态性(single nucleotide polymorphism,SNP)在哮喘组和对照组相比差异有统计学(OR=3.405,95%CI 1.214～9.551,P3、Rs10053538位点基因型频数及等位基因频数分布差异均无统计学意义(P>0.05);单体型T-C-G在两组中差异有统计学意义(P=0.029,OR=3.232,95%CI 1.066～9.796);分别比较各位点CVA患儿不同基因型的皮肤点刺、总IgE、EOS水平,并未发现有统计学差异的指标(P>0.05)。结论 tim-3启动子区的Rs1051746与儿童咳嗽变异性哮喘易感性相关,携带T-C-G单体型的人群罹患CVA的风险性可能较正常人群高,各位点基因多态性可能与皮肤点刺、总IgE、EOS水平无关。

关键词：儿童咳嗽变异性哮喘单核苷酸多态性 tim-3 单体型

tim-3 mediated NK-CD8+ T cells cross talk in chronic hepatitis B

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tim-3 expression define a population of CD4 T cells with regulatory T cell phenotype that inhibit autologous CD8 T cells in Hepotocelluar carcinoma

2012全国临床微生物与感染免疫学术研讨会

作者： Zhao Di,Liang Xiaohong,Gao Lifen,Ma Chunhong Institute of Immunology,Shandong University School of Medicine,44 Wenhua Xi Road,Jinan,Shandong,250012 P.R.China

Background & Aims T cell immunoglobulin and mucin domain-3(tim-3) has been widely known as immune regulator which plays an important role in various disease,including viral infection *** previously reported the repression of tim-3 on NK cells in CHB *** this study,we characterized the role of tim-3 on NK-CD8 T cells cross talk in chronic hepatitis B infection. Methods 111 CHB patients,34 healthy controls are enrolled for investigating tim-3 expression and regulation on CD8 T cells by flow *** collected from CHB patients were treated with HBs peptide and the IFN-gamma and proliferation of CD8 T cells were *** antibody against tim-3 and lactose were involved in assay the effect of tim-3 pathway on CD8 T *** involvement of NK cells in the tim-3 mediated suppression on CD8 T cells were evaluated by NK depletion. Results tim-3 expression was significantly up-regulated on CD8 T cells which significantly correlated with HBV viral ***-3 expressing CD8 T cells had a higher expression of activated maker CD69 but failed to produce IFN-gamma,Granzyme B,perforin or proliferate in response to HBs-antigen peptide or anti-human CD3 and anti-human CD28,indicating the negative role of tim-3 on CD8 T ***,blocking tim-3 pathway in PBMCs enhanced HBV specific IFN-γexpression and proliferation in CD8 T cells of CHB patients. However,blocking tim-3 pathway didn’t change HBs-stimulated IFN-7 expression of purified CD8 T cells from CHB *** of NK cells destroyed the tim-3 mediated suppression on HBV specific IFN-γexpression and proliferation in CD8 T ***-PCR and flow cytometry results showed the expression of tim-3 ligand, galectin-9 inNK *** of lactose which blocks galectins significantly increased the activity of CD8 T cells from CHB patients. Conclusions Chronic HBV infection increased the tim-3 expression on CD8 T cells which in turn inhibited CD8 T cells to produce IFN-γand proliferate

关键词： tim-3 Hep otitis B Negative regulation CD8+ T cells NK cells

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Tim-3 expression define a population of CD4 T cells with reg...

tim-3 Inhibits Macrophage Activity In Echinococcus granulosus Infected Mice

第八届全国免疫学学术大会

作者： Jing Yan Yi Zhang Jing-Ping Zhang Limin Zheng State Key Laboratory of Oncology in South China Sun Yat-sen University Cancer Center

T cell immunoglobulin and mucin domain containing molecule-3(tim-3) was originally identified as a marker expressed on activated Th1 cell *** it was reported that this protein negatively regulates the immune responses against viral infection and has implications for autoimmune ***, the role of tim-3+ CD4 T cells in human tumor remains largely *** investigate the expression and function of tim-3+ CD4 T cells in human hepatocellular carcinoma(HCC), we compared the expression level of tim 3 in CD4 T cells from nontumor-infiltrating lymphocytes(NIL), tumor-infiltrating lymphocytes(TIL), as well as peripheral blood from HCC patients and healthy *** percentages of tim-3+ CD4 T cells were found in the peripheral blood from HCC patients and healthy donors, while more tim-3+ CD4 T cells were found in TIL when comparing with the corresponding ***, tim-3+ CD4 T cells in tumor tissue produced less T helper 1 type cytokines such as IFN-γ or IL-2 relative to tim-3- CD4 T ***, tim-3+ CD4 T cells from TIL define a population of functional CD25+CD127lowFoxp3+ regulatory T cells(Treg) that could suppress autologous CD8 T cell proliferation and cytokine ***, our data indicate that tim-3+ CD4 T cells function as a negative regulator in anti-tumor response and contribute to immune suppressive microenvironment in ***, targeting tim-3 in Treg may help to develop novel strategy for HCC immunotherapy.

关键词： Hepatocellular carcinoma tumor immunoediting tim-3 Treg

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Tim-3 Inhibits Macrophage Activity In Echinococcus granulosu...

Galectin-9(tim-3L)显著减弱小鼠移植排斥

第九届全国免疫学学术大会

作者： Jun Hou Fangjie Xu Shuanghong Yin Hairui Fang Hongqun Jiang Xiangwei Wu Xueling Chen Department of Immunology School of MedicineShihezi University

Background:The expression levels of tim-3(T cell immunoglobulin domain and mucin domain-containing molecule-3),a newly discovered immunomodulatory molecule,in the early stages of Echinococcus granulosus infection in mice are not *** establishing animal models of Echinococcus granulosus(***)infected mice,we explored whether *** promoted tim-3 upregulation in macrophages,and then inhibits their ***:Ba1b/c mice were infected with *** macrophages and spleen cells were collected at 1,5,9 and 13 days *** the indicated time points,levels of tim-3 in peritoneal macrophages and spleen CD3+lymphocyte subsets were detected by flow ***:*** expression levels of tim-3 of spleen macrophages(9,13 days)and peritoneal macrophage(5,9,13 days)were much higher in ***-infected group than those in control group with statistical significance(Ptim-3 expression levels of CD3spleen lymphocyte subsets between ***-infected group and control group was not significant(P>0.05).*** numbers of spleen macrophage and peritoneal macrophages keep no change except transient increase in spleen macrophage(9 days).Conclusion:During early stage of *** infection in mice,the levels of tim-3 expression were upregulated,which might inhibit the function of macrophages and result in host-immunity-defensive-system inhibition and immune tolerance of *** to host.

关键词： tim-3 Echinococcus Granulosus Macrophage

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中华微生物学和免疫学杂志 2009年第1期29卷 5-10页

作者：何文涛袁劲方泽民汪峰徐逸周鸿敏高英张维娜王璐陈忠华华中科技大学同济医学院附属同济医院器官移植研究所教育部/卫生部重点实验室

目的探究Galectin-9(即T cell immunoglobulin domain and mucin domain protein-3 ligand,tim-3L)的真核定位与功能,及其对同种异基因排斥反应的影响。方法PCR扩增Galectin-9片段,插入到pEGFP-N1质粒,转染中国仓鼠卵巢癌细胞系(CHO)行G418筛选,分选增强型绿色荧光蛋白(EGFP)阳性细胞。免疫组化检测Galectin-9的表达,Alamar Blue法检测稳定转染Galectin-9的CHO细胞及其新鲜培养上清对脾细胞增殖的影响,ELISA检测IL-2水平。给予BALB/c→C57BL/6心脏移植受鼠Galectin-9蛋白100μg×7 d。结果Galectin-9表达于细胞浆,稳定转染Galectin-9-EGFP的CHO细胞上清抑制淋巴细胞增殖和IL-2的产生。上述效应可被tim-3-Fc融合蛋白逆转。Galectin-9干预的心脏移植物中位生存时间明显延长[(22.7±1.2)d,(7.2±0.4)d)]。结论真核细胞中Galectin-9可通过分泌形式负调节同种异基因免疫;Galectin-9有望成为新型的抗排斥药物。

关键词： tim-3 Galectin-9 免疫抑制小鼠