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作 者:卢杨 孙汭[1] 田志刚[1] 陈永艳[1] LU Yang;SUN Rui;TIAN Zhigang;CHEN Yongyan(Institute of Immunology,University of Science and Technology of China,Hefei 230027,China)
机构地区:[1]中国科学技术大学免疫学研究所,合肥230027
出 处:《中国免疫学杂志》2022年第2期129-134,共6页Chinese Journal of Immunology
基 金:中科院先导项目(XDB29030201);国家重点研发计划(2018YFA0507403,2019YFA0508502);NSFC基础科学中心项目(81788101)。
摘 要:目的:探究抑制性受体TIGIT在HBV免疫应答中的作用及靶向TIGIT在HBV免疫治疗中的可能应用。方法:利用高压注射pAAV-HBV1.2质粒获得HBV携带小鼠,利用流式细胞术分析NK细胞和T细胞上TIGIT的表达。通过单克隆抗体阻断和基因缺陷验证TIGIT在HBV免疫应答中的作用。结果:HBV携带小鼠NK细胞和T细胞显著上调表达TIGIT;抗体阻断TIGIT后HBV携带小鼠血清HBsAg水平显著降低,且HBsAg转阴率增高。抗体阻断TIGIT增加肝脏中NK细胞及T细胞数量并增强其分泌细胞因子的功能。TIGIT分子的缺陷亦导致HBV携带小鼠血清HBsAg水平显著降低。结论:靶向阻断TIGIT在HBV免疫治疗中具有潜在的应用价值。Objective:To explore the role of inhibitory receptor TIGIT in immune response to HBV and the potential application of targeting TIGIT in HBV immunotherapy.Methods:Hydrodynamic injection of pAAV-HBV1.2 plasmid was used to obtain HBVcarrier mice.The expression of TIGIT on NK and T cells was analyzed by flow cytometry.The role of TIGIT in HBV immune response was investigated by mAb blockade and gene deficiency.Results:NK and T cells of HBV-carrier mice significantly up-regulated the expression levels of TIGIT.After anti-TIGIT mAb blocking,the serum levels of HBsAg were significantly reduced in the HBV-carrier mice,and the HBsAg clearance was accelerated.Anti-TIGIT mAb blocking increased the number of NK and T cells in the liver and enhanced their production of cytokines.The deficiency of TIGIT also led to a significant decrease in the serum levels of HBsAg in the HBV-carrier mice.Conclusion:Targeting TIGIT is promising for HBV immunotherapy.
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