hMSH2参与Vγ9δ2T细胞介导的胃癌细胞株杀伤作用  

MutS homolog 2 plays a role in Vγ9δ2 T cell-mediated anti-gastric carcinoma immunity

作　　者：代玉梅 陈慧[2] 莫辰[2] 师敬飞[2] 刘云峰 李文利 崔莲仙[2] 何维[2] 

机构地区：[1]广州市妇女儿童医疗中心临床检验部,510623 [2]北京协和医学院免疫学系&中国医学科学院基础医学研究所,100005

出　　处：《中华微生物学和免疫学杂志》2014年第7期521-526,共6页Chinese Journal of Microbiology and Immunology

基　　金：国家自然科学基金重点项目（30930083）;广东省自然科学基金博士启动项目（S2013040015845）;广州市医药卫生科技项目（20131A011048）

摘　　要：目的：探讨Vγ9δ2 T细胞识别的肿瘤相关内源性新蛋白质配体MutS同源蛋白2（hMSH2）在胃癌免疫中的作用与意义。方法通过特异性抗体阻断胃癌细胞膜异位表达的hMSH2分子，观察Vγ9δ2 T细胞杀伤功能变化及IFN-γ和TNF-α分泌情况；使用肿瘤组织芯片（ TMA）免疫组化染色分析hMSH2在胃癌中的亚细胞分布。结果 hMSH2在胃癌细胞中存在较高水平的膜异位表达；anti-hMSH2抗体封闭后， Vγ9δ2 T 细胞对胃癌细胞的杀伤效率显著降低， IFN-γ分泌减少， TNF-α分泌则增多；hMSH2在不同类型、不同分期的胃癌组织中均呈异常的细胞膜、细胞质分布，但细胞核表达并未明显减低或缺失，作为非癌对照的浅表性胃炎组织标本hMSH2表达亦明显增强。结论异位表达的hMSH2可作为内源性应激性配体促进Vγ9δ2 T细胞杀伤胃癌细胞及分泌IFN-γ，在胃癌固有免疫中具有重要意义。Objective To study the role of human MutS homolog 2 （hMSH2）, a newly identified protein ligand that was recognized by Vγ9δ2 T cells , in innate anti-gastric carcinoma immunity .Methods Flow cytometry and laser confocal microscopy were used to identify hMSH 2 that ectopically expressed on gas-tric carcinoma cell line 803.An anti-hMSH2 antibody was used to block hMSH2 to evaluate its effects on the cytotoxicity of Vγ9δ2 T cells and their cytokines secretion .Subcellular distribution of hMSH 2 in gastric car-cinoma tissues was examined by tissue microarray immunohistochemistry analysis .Results Ectopic mem-brane expression of hMSH 2 was observed on 803 cells at a relatively high level .Vγ9δ2 T cells blocked with specific anti-hMSH2 antibody showed a decreased cytotoxicity and a reduced IFN-γbut an increased TNF-αsecretion.Ectopic expression of hMSH2 was found in various types of gastric carcinoma tissues at different stages.Enhanced expression of hMSH2 was detected in specimens collected from patients with chronic super-ficial gastritis.Conclusion Ectopically expressed hMSH2 served as a stress-induced endogenous ligand which could promote the cytotoxicity of Vγ9δ2 T cells against gastric carcinoma cells and enhance their IFN-γsecretion.hMSH2 played an essential role in innate anti-gastric carcinoma immunity .

关 键 词：人MutS同源蛋白2 Vγ9δ2T细胞 胃癌 固有免疫 

分 类 号：R735.2[医药卫生—肿瘤]