Fukushima A, Fukata K, Ozaki A, Takata M, Kuroda N, Enzan H, Ueno H
Laboratory of Immunology, Department of Ophthalmology, Kochi Medical School, Kohasu, Oko-cho, Nankoku City, Japan.
Br J Ophthalmol. 2002 Oct;86(10):1166-71. doi: 10.1136/bjo.86.10.1166.
BACKGROUND/AIMS: Interferon gamma (IFN-gamma) knockout mice exhibit severe allergic conjunctivitis (AC), indicating that IFN-gamma regulates the development of AC. The authors examined whether this inhibitory effect of IFN-gamma is exerted during the induction or effector phase of experimental AC.
Experimental immune mediated blepharoconjunctivitis (EC) was induced in Brown Norway (BN) rats, using ovalbumin (OVA) as the antigen. To investigate the role of IFN-gamma in the induction phase, EC was induced by active immunisation and IFN-gamma (10 micro g/time, total 70 micro g), or phosphate buffered saline (PBS) as a control, was injected intraperitoneally every other day from the day of immunisation. The rats were challenged with OVA eye drops 13 days after immunisation, and 24 hours later, the eyes were harvested for histology. To examine the effects of IFN-gamma in the effector phase, OVA specific T cells were transferred into syngeneic rats and IFN-gamma (10 micro g/time, total 50 micro g) or PBS was injected each day after the transfer until induction of EC 4 days later with an OVA challenge. To investigate the role of endogenous IFN-gamma during the effector phase, an anti-IFN-gamma monoclonal antibody (3 mg/time) was injected on days 3 and 4.
Injection of IFN-gamma into actively immunised rats suppressed eosinophilic infiltration but not infiltration of mononuclear cells. In contrast, neither IFN-gamma nor anti-IFN-gamma affected EC in passively immunised rats.
IFN-gamma is a suppressive cytokine for the development of EC and exerts this suppressive effect during the induction phase.
背景/目的:γ干扰素(IFN-γ)基因敲除小鼠表现出严重的变应性结膜炎(AC),这表明IFN-γ调节AC的发展。作者研究了IFN-γ的这种抑制作用是在实验性AC的诱导期还是效应期发挥的。
以卵清蛋白(OVA)为抗原,在棕色挪威(BN)大鼠中诱导实验性免疫介导的睑结膜炎(EC)。为研究IFN-γ在诱导期的作用,通过主动免疫诱导EC,并从免疫当天起每隔一天腹腔注射IFN-γ(10μg/次,共70μg)或磷酸盐缓冲盐水(PBS)作为对照。免疫13天后用OVA滴眼液攻击大鼠,24小时后摘取眼球进行组织学检查。为检测IFN-γ在效应期的作用,将OVA特异性T细胞转移至同基因大鼠体内,并在转移后每天注射IFN-γ(10μg/次,共50μg)或PBS,直至4天后用OVA攻击诱导出EC。为研究效应期内内源性IFN-γ的作用,在第3天和第4天注射抗IFN-γ单克隆抗体(3mg/次)。
向主动免疫的大鼠注射IFN-γ可抑制嗜酸性粒细胞浸润,但不影响单核细胞浸润。相反,IFN-γ和抗IFN-γ均不影响被动免疫大鼠的EC。
IFN-γ是EC发展的抑制性细胞因子,并在诱导期发挥这种抑制作用。