CAJ | 학술논문

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。
목적：탐토Vγ9δ2 T세포식별적종류상관내원성신단백질배체MutS동원단백2（hMSH2）재위암면역중적작용여의의。방법통과특이성항체조단위암세포막이위표체적hMSH2분자，관찰Vγ9δ2 T세포살상공능변화급IFN-γ화TNF-α분비정황；사용종류조직심편（ TMA）면역조화염색분석hMSH2재위암중적아세포분포。결과 hMSH2재위암세포중존재교고수평적막이위표체；anti-hMSH2항체봉폐후， Vγ9δ2 T 세포대위암세포적살상효솔현저강저， IFN-γ분비감소， TNF-α분비칙증다；hMSH2재불동류형、불동분기적위암조직중균정이상적세포막、세포질분포，단세포핵표체병미명현감저혹결실，작위비암대조적천표성위염조직표본hMSH2표체역명현증강。결론이위표체적hMSH2가작위내원성응격성배체촉진Vγ9δ2 T세포살상위암세포급분비IFN-γ，재위암고유면역중구유중요의의。
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 .