【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。更多还原

【Abstract】 ObjectiveHerpetic 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.MethodsCorneas of right eyes from 90 BALB/c mice were infected with 10~ 6 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.ResultsAs measured by flow cytometry,in the mice treated with OX40-Ig,78.2 of CD4~ + T cells were reduced.83.3 of the HSV-1-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.ConclusionThe 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.更多还原