Herz U, Gerhold K, Grüber C, Braun A, Wahn U, Renz H, Paul K
Departments of Laboratory Medicine and Pathobiochemistry and Pediatric Pulmonology and Immunology, Charité, Campus Virchow-Clinic, Berlin, Germany.
J Allergy Clin Immunol. 1998 Nov;102(5):867-74. doi: 10.1016/s0091-6749(98)70030-2.
Epidemiologic studies suggest an inverse correlation between infections and development of atopy. The purpose of this study was to test the hypothesis whether a preexisting Th1-type immune response elicited by BCG immunization could suppress allergic sensitization and airway hyperreactivity in an animal model.
BALB/c mice were immunized with BCG and/or sensitized to ovalbumin.
BCG immunization alone resulted in cutaneous type-IV hypersensitivity reactions to tuberculin and granulomatous lesions in the liver. Splenic mononuclear cells (MNCs) produced increased levels of IFN-gamma after activation by Concanavalin A (ConA). Ovalbumin sensitization alone resulted in increased production of IL-4 after activation by ConA. Ovalbumin-sensitized animals also demonstrated markedly elevated anti-ovalbumin IgE/IgG1 serum antibody titers and increased airway reactivity after allergen challenges by means of the airways. BCG immunization 14 days before the start of ovalbumin sensitization markedly hindered the development of allergic responses as indicated by (1) increased IFN-gamma and normalized IL-4 and IL-10 production by splenic MNCs after activation with ConA, (2) a reduced proliferation rate of splenic MNCs after ovalbumin restimulation, (3) partial prevention of ovalbumin-specific IgE/IgG1 serum antibody titers but elevated (nonallergic) anti-ovalbumin IgG2a serum antibody titers, (4) prevention of airway responsiveness, (5) reduced eosinophilic influx into the airway lumen, and (6) reduced levels of IL-4 and IL-5 in broncho alveolar lavage fluids.
In this model BCG immunization established a Th1-type immune response that hinders allergic sensitization and the development of increased airway reactivity.
流行病学研究表明感染与特应性疾病的发生呈负相关。本研究的目的是验证卡介苗免疫引发的预先存在的Th1型免疫反应是否能在动物模型中抑制过敏性致敏和气道高反应性这一假说。
用卡介苗免疫BALB/c小鼠和/或使其对卵清蛋白致敏。
单独卡介苗免疫导致对结核菌素的皮肤IV型超敏反应和肝脏肉芽肿性病变。脾单核细胞（MNC）经刀豆蛋白A（ConA）激活后产生的γ干扰素水平升高。单独卵清蛋白致敏导致经ConA激活后白细胞介素-4的产生增加。卵清蛋白致敏的动物在经气道进行过敏原激发后还表现出抗卵清蛋白IgE/IgG1血清抗体滴度显著升高以及气道反应性增强。在卵清蛋白致敏开始前14天进行卡介苗免疫显著阻碍了过敏反应的发展，表现为：（1）脾MNC经ConA激活后γ干扰素增加，白细胞介素-4和白细胞介素-10产生恢复正常；（2）卵清蛋白再次刺激后脾MNC的增殖率降低；（3）部分预防了卵清蛋白特异性IgE/IgG1血清抗体滴度，但抗卵清蛋白IgG2a血清抗体滴度升高（非过敏性）；（4）预防了气道反应性；（5）减少了嗜酸性粒细胞向气道腔内的流入；（6）支气管肺泡灌洗液中白细胞介素-4和白细胞介素-5水平降低。
在该模型中，卡介苗免疫建立了一种Th1型免疫反应，可阻碍过敏性致敏和气道反应性增强的发展。
