OX40-Ig融合蛋白对鼠单纯疱疹性角膜基质炎的抑制作用  

Inhibition of OX40-Ig on herpetic stromal keratitis in murine model

作　　者：夏丽坤[1] 陈晓隆[1] 朱英明[1] 周晶[1] 

机构地区：[1]中国医科大学第二附属医院眼科,沈阳110004

出　　处：《眼科研究》2006年第5期479-483,共5页Chinese Ophthalmic Research

基　　金：辽宁省教育厅基金资助(2004D163)

摘　　要：目的研究OX40-Ig融合蛋白对鼠单纯疱疹性角膜基质炎(HSK)的免疫抑制作用。方法将1×106PFU的单纯疱疹病毒1型(HSV-1)Mckrae毒株接种于BALB/c鼠的角膜上建立HSK模型;分别于接种病毒的当天、接种后第2、4d将OX40-Ig融合蛋白100μg注射到鼠的腹膜下,观察OX40-Ig融合蛋白对鼠HSK的影响。结果OX40-Ig融合蛋白使鼠外周血中CD4+T细胞减少了78·2%,使鼠HSK发病率由83·3%下降到20·0%。OX40-Ig治疗组的小鼠角膜基质混浊程度较对照组明显减轻,角膜内炎性细胞浸润也明显减少,迟发型超敏反应能力显著下降。结论OX40-Ig融合蛋白能够阻断OX-40/OX-40L协同刺激途径,抑制CD4+T细胞增生,阻止HSK的发病,减轻HSK的严重程度。Objective Herpetic stromal keratitis （HSK） is an immunoinflammatory lesion in the cornea of the eye set off by the infection with HSV-1. The disease appears to be orchestrated by CD4~ T cells. In current study, we investigated the inhibition of OX40-Ig on the inhibition of HSK. Methods Corneas of right eyes from 90 BALB/c mice were infected with 106 PFU of HSV-1 McKrae strain. Mice were injected intraperitoneally with OX40-Ig or IgG Fc or PBS given on day 0,2,4 after the infection. CD4 ~ T cells from peripheral blood of mice were analyzed on FACS 440 analyzer. The clinical evaluations of infected eyes were taken under the slit-lamp microscope, and the histological changes of corneas were observed under the optical microscope. Virus titers in corneas after HSV-1 infection were tested with VERO cells, and delayed type hypersensitivity was observed. The effects of OX40-Ig on HSK were evaluated. Results As measured by flow cytometry,in the mice treated with OX40-Ig,78.2% of CD4 ~ T cells were reduced. 83.3% of the HSV-l-infected control mice developed severe stromal keratitis, but only 20.0% of mice treated by OX40-Ig developed HSK. Lesions in OX40-Ig treated mice showed markedly reduced severity by slit-lamp microscope, and histologically the corneal stroma had a decrease in inflammatory cell infiltration compared to the control group, and the delayed type hypersensitivity was reduced. Conclusion The results provide an evidence that blockade of OX-40/OX-40L costimulation by OX40-Ig can inhibit the proliferation of CD4^＋ T cells and impair onset and severity of HSK.

关 键 词：角膜 单纯疱疹病毒 协同刺激分子 角膜基质炎 免疫病理 

分 类 号：R772.2[医药卫生—眼科]