Vandebriel Rob J, Gremmer Eric R, van Hartskamp Michiel, Dormans Jan A M A, Mooi Frits R
Laboratory for Toxicology, Pathology and Genetics, National Institute of Public Health and the Environment, P.O. Box 1, 3720 BA Bilthoven, The Netherlands.
Clin Vaccine Immunol. 2007 Mar;14(3):211-9. doi: 10.1128/CVI.00306-06. Epub 2007 Jan 3.
We have previously shown that in mice, diphtheria-tetanus-acellular pertussis (DTaP) vaccination before Bordetella pertussis infection resulted in, besides effective clearance, immediate hypersensitivity (lung eosinophilia, increased total serum immunoglobulin E [IgE], and increased ex vivo Th2 cytokine production by cells from the bronchial lymph nodes). To better appreciate the extent of these findings, we measured DTaP vaccination effects in the local lymph node assay (LLNA) and an ovalbumin (OVA) lung allergy model. In the LLNA, mice were vaccinated or adjuvant treated before being sensitized with trimellitic anhydride (TMA; inducing a Th2-directed response) and dinitrochlorobenzene (DNCB; inducing a Th1-directed response). Compared to the adjuvant-treated controls, the vaccinated mice showed a decreased response to TMA and (to a much lesser extent) an increased response to DNCB. The decreased response to TMA coincided with increased transforming growth factor beta levels. With the exception of filamentous hemagglutinin, all vaccine constituents contributed to the decreased response to TMA. In the lung allergy model, sensitization induced OVA-specific IgE, lung pathology (peribronchiolitis, perivasculitis, and hypertrophy of the bronchiolar mucus cells) and increased the number of eosinophils, lymphocytes, and neutrophils in the bronchoalveolar lavage fluid. Vaccination failed to modulate these parameters. In conclusion, although DTaP vaccination may affect the LLNA response, we found no evidence of an effect on lung allergy.
我们之前已经表明,在小鼠中,百日咳博德特氏菌感染前接种白喉-破伤风-无细胞百日咳(DTaP)疫苗,除了能有效清除病原体外,还会引发速发型超敏反应(肺部嗜酸性粒细胞增多、血清总免疫球蛋白E [IgE] 增加以及支气管淋巴结细胞的体外Th2细胞因子产生增加)。为了更好地理解这些发现的程度,我们在局部淋巴结试验(LLNA)和卵清蛋白(OVA)肺部过敏模型中测量了DTaP疫苗接种的效果。在LLNA中,小鼠在被偏苯三酸酐(TMA;诱导Th2主导的反应)和二硝基氯苯(DNCB;诱导Th1主导的反应)致敏之前先进行疫苗接种或佐剂处理。与佐剂处理的对照组相比,接种疫苗的小鼠对TMA的反应降低,而对DNCB的反应(程度小得多)增加。对TMA反应的降低与转化生长因子β水平的增加同时出现。除丝状血凝素外,所有疫苗成分都导致对TMA的反应降低。在肺部过敏模型中,致敏诱导了OVA特异性IgE、肺部病理变化(细支气管周围炎、血管周围炎和细支气管黏液细胞肥大),并增加了支气管肺泡灌洗液中嗜酸性粒细胞、淋巴细胞和中性粒细胞的数量。疫苗接种未能调节这些参数。总之,虽然DTaP疫苗接种可能会影响LLNA反应,但我们没有发现其对肺部过敏有影响的证据。