T细胞免疫球蛋白黏蛋白分子3对单纯疱疹性角膜基质炎的免疫调节作用  

Immunoregulation effects of T cell immunoglobulin and mucin-domain-containing mo-lecule-3 on herpetic stromal keratitis

作　　者：夏丽坤[1] 李琰[1] 张胜男[1] 周佳子[1] 

机构地区：[1]中国医科大学附属盛京医院眼科,辽宁省沈阳市110004

出　　处：《眼科新进展》2009年第10期730-734,共5页Recent Advances in Ophthalmology

基　　金：国家自然科学基金面上项目基金资助(编号:30772394);辽宁省自然科学基金资助(编号:20072091);辽宁省科技攻关计划项目基金资助(编号:2007225018);沈阳市科学技术计划项目基金资助(编号:1091171-1-02)~~

摘　　要：目的研究T细胞免疫球蛋白黏蛋白分子3(T cell immunoglobulin and mucin-do-main-containing molecule-3,Tim-3)在小鼠单纯疱疹性角膜基质炎(herpetic stromal keratitis,HSK)发病机制中的免疫调节作用。方法将1.0×106空斑单位的单纯疱疹病毒1型KOS毒株接种于BALB/c鼠的角膜上,建立HSK动物模型;在角膜接种病毒的同时将抗Tim-3单克隆抗体100μg注射到aTim-3组小鼠的腹膜腔内作为aTim-3组;ISO对照组和NS对照组小鼠腹膜腔内注射非特异性免疫球蛋白同型对照抗体ISO100μg或等容积的生理盐水。在裂隙灯显微镜下观察角膜的变化,检查角膜的组织学病理改变,用VERO细胞检测角膜病毒滴度,并行小鼠迟发型超敏反应(delayedtypehypersensitivity,DTH)检测和脾细胞体外分泌细胞因子的检测。结果腹膜腔内注射抗Tim-3单克隆抗体的小鼠,角膜基质内炎性细胞较对照组小鼠明显增多、角膜混浊程度也较对照组小鼠明显严重(P均<0.01)、DTH值(1.025±0.088)mm明显强于ISO对照组和NS对照组[DTH值分别为(0.651±0.051)mm和(0.642±0.064)mm],差异均具有显著统计学意义(P均<0.01);同时,腹膜腔内注射了抗Tim-3单克隆抗体的小鼠,脾细胞分泌Th1型细胞因子IFN-γ的量(25.36±3.65)μg.L-1明显多于ISO对照组和NS对照组[分别为(19.23±1.82)μg.L-1和(18.73±0.98)μg.L-1],差异均具有显著统计学意义(P均<0.01);但腹膜腔内注射抗Tim-3单克隆抗体未影响小鼠角膜内病毒复制及小鼠HSK发病率和小鼠死亡率。结论Tim-3作为一个免疫调节分子,通过抑制Th1型免疫反应,调节HSK的疾病程度。Objective To investigate the immunoloregulation effects of T cell immunoglobulin and mucin-domain-containing molecule-3（Tim-3） on pathogenesis of herpetic stromal keratitis（HSK） in mice.Methods HSK models were established with inoculating herpes simplex virus type 1 KOS strain at 100×103 plague forming unit to corneas of BALB/c mice.Meanwhile,100 μg anti-Tim-3 monoclonal antibody（anti-Tim-3 mAb） was injected intraperitoneally as aTim-3 group,and 100 μg homoeotypic nonspecific immune globulin contrast antibody ISO or isometric normal sodium was injected intraperitoneally as ISO control group or NS control group.Corneal changes were observed under slit lamp microscope to examine the histopathological changes of corneas.Virus titers in corneas were tested with VERO cells.Delayed type hypersensitivity（DTH） and detection of exocrine cytokines of splenocytes were taken.Results For the mice injecting anti-Tim-3 mAb intraperitoneally,inflammatory cells in corneal stroma significantly increased and the degree of corneal opacity degree became more severe compared with those of control groups（both P〈0.01）,DTH（1.025±0.088）mm was higher than ISO control group（0.651±0.051）mm and NS control group（0.642±0.064）mm（both P〈0.01）;The quantity of IFN-γ in Th1 cytokines secreted by splenocytes（25.36±3.65）μg·L-1 was obviously higher than that of ISO control group（18.73±0.98）μg·L-1 and that of NS control group（19.23±1.82）μg·L-1（both P〈0.01）.However,anti-Tim-3 mAb injected intraperitoneally did not influence the replication of virus in cornea,morbidity and mortality of HSK mice.Conclusion Tim-3 as an immunoregulatory molecule is involved in regulating the degree of HSK by inhibiting Th1 type immunological reaction.

关 键 词：单纯疱疹病毒 角膜基质炎 角膜 TH1细胞 T细胞免疫球蛋白黏蛋白分子3 

分 类 号：R772.2[医药卫生—眼科]