Cutting edge: Eosinophils do not contribute to respiratory syncytial virus vaccine-enhanced disease.
Cutting edge: Eosinophils do not contribute to respiratory syncytial virus vaccine-enhanced disease.
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DOI：
10.4049/jimmunol.181.10.6692
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发表时间：
2008-11-15
期刊：
影响因子：
--
通讯作者：
Varga SM
中科院分区：
文献类型：
--
作者：
Castilow EM;Legge KL;Varga SM
用表达呼吸道合胞病毒（RSV）附着（G）蛋白的重组痘苗病毒（vacv）预先免疫的BALB/c小鼠感染RSV后，会导致肺部嗜酸性粒细胞增多，这类似于接种FI - RSV疫苗的儿童的反应，同时体重减轻加剧、临床疾病加重以及增强的暂停时间（Penh）增加。我们发现，用vacvG预先免疫的嗜酸性粒细胞缺陷小鼠感染RSV后，体重减轻加剧、临床疾病加重以及Penh增加的情况与野生型对照组相似。这些RSV疫苗增强性疾病的指标依赖于STAT4。有趣的是，两种最常见的激活STAT4的细胞因子IL - 12和IL - 23都并非疾病发展所必需的。我们证明，STAT4激活后产生的干扰素 - γ会导致临床疾病加重和Penh增加，但不会导致体重减轻。我们的研究结果对未来RSV疫苗的设计具有重要意义，表明增强Th1反应可能会加重疾病。
Respiratory syncytial virus (RSV) infection of BALB/c mice previously immunized with a recombinant vaccinia virus (vacv) expressing the attachment (G) protein of RSV results in pulmonary eosinophilia, which mimics the response of FI-RSV vaccinated children, as well as increased weight loss, clinical illness, and Penh. We show that RSV infection of eosinophil-deficient mice previously immunized with vacvG results in the development of increased weight loss, clinical illness, and Penh that is similar to wild-type controls. These measures of RSV vaccine-enhanced disease are dependent upon STAT4. Interestingly, neither IL-12 nor IL-23, the two most common STAT4-activating cytokines, proved necessary for the development of disease. We demonstrate that IFN-γ, which is produced following STAT4 activation, contributes to clinical illness and increased Penh, but not weight loss. Our results have important implications for future RSV vaccine design suggesting that enhancing a Th1 response may exacerbate disease.
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影响因子：
32.4
作者：
Oppmann, B;Lesley, R;Kastelein, RA
通讯作者：
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影响因子：
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作者：
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DOI：
10.1084/jem.181.5.1755
发表时间：
1995-05-01
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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32.4
作者：
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影响因子：
5.4
作者：
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