Sher A, Coffman R L, Hieny S, Cheever A W
Immunology and Cell Biology and Host-Parasite Relations Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
J Immunol. 1990 Dec 1;145(11):3911-6.
To investigate the role of anaphylactic immune responses in protective immunity against schistosomiasis, mice vaccinated with irradiated cercariae of Schistosoma mansoni were treated with neutralizing mAb antibodies against either IL-5 or IL-4 before and during challenge infection. Anti-IL-5-treated vaccinated mice showed a complete ablation of circulating as well as tissue eosinophils present in inflammatory reactions to migrating schistosomula in the skin and lungs but nevertheless eliminated challenge infections as effectively as vaccinated animals treated with a control mAb. Similarly, treatment of vaccinated mice with an anti-IL-4 mAb markedly reduced serum IgE although failing to diminish immunity. The effect of anti-IL-5 mediated eosinophil depletion was also assessed in a second model in which resistance is induced by concomitant chronic infection. Again, normal, unaltered protection was observed in the absence of circulating and tissue eosinophils. In contrast to the above findings, treatment with anti-IFN-gamma was found to cause a partial depletion of immunity in vaccinated mice whereas, paradoxically, increasing the numbers of inflammatory reactions against invading schistosomula in the lungs. These observations argue against a requirement for either eosinophils or IgE in the anti-schistosome immunity induced by vaccination with irradiated cercariae or for eosinophils in the resistance resulting from previous infection in mice and support previous data suggesting a role for an IFN-gamma dependent cell-mediated effector mechanism in vaccine-induced resistance.
为了研究过敏免疫反应在血吸虫病保护性免疫中的作用,在用曼氏血吸虫辐照尾蚴接种的小鼠在攻击感染前及感染期间,用抗IL-5或抗IL-4的中和单克隆抗体进行处理。用抗IL-5处理的接种疫苗小鼠,其循环以及在皮肤和肺中对移行的血吸虫幼虫炎症反应中存在的组织嗜酸性粒细胞完全消失,但仍能像用对照单克隆抗体处理的接种动物一样有效地清除攻击感染。同样,用抗IL-4单克隆抗体处理接种疫苗小鼠,血清IgE明显降低,尽管未能减弱免疫力。在另一种由伴随慢性感染诱导抗性的模型中,也评估了抗IL-5介导的嗜酸性粒细胞耗竭的效果。同样,在没有循环和组织嗜酸性粒细胞的情况下,观察到正常、未改变的保护作用。与上述发现相反,发现用抗IFN-γ处理会导致接种疫苗小鼠的免疫力部分耗竭,而矛盾的是,这会增加肺部针对入侵血吸虫幼虫的炎症反应数量。这些观察结果表明,在用辐照尾蚴接种诱导的抗血吸虫免疫中,嗜酸性粒细胞或IgE并非必需,在小鼠先前感染产生的抗性中嗜酸性粒细胞也非必需,并支持先前的数据,表明IFN-γ依赖性细胞介导的效应机制在疫苗诱导的抗性中起作用。