Differential role of gamma interferon in inhibiting pulmonary eosinophilia and exacerbating systemic disease in fusion protein-immunized mice undergoing challenge infection with respiratory syncytial virus
Differential role of gamma interferon in inhibiting pulmonary eosinophilia and exacerbating systemic disease in fusion protein-immunized mice undergoing challenge infection with respiratory syncytial virus
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DOI：
10.1128/jvi.01949-07
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发表时间：
2008-03-01
影响因子：
5.4
通讯作者：
Vargal, Steven M.
中科院分区：
文献类型：
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作者：
Castilow, Elaine M.;Olson, Matthew R.;Vargal, Steven M.
继发呼吸道合胞病毒（RSV）的接触可导致接种疫苗的个体的免疫病理学和疾病增强。带有单个RSV蛋白的疫苗接种会影响在挑战RSV感染以及免疫病理学程度下发展的二级RSV特异性免疫反应的类型。 RSV特异性的记忆CD4 T细胞可以通过其细胞因子产生直接有助于免疫病理学。用重组疫苗病毒（VV）对BALB/C小鼠进行免疫接收，表达RSV的附着蛋白（G）蛋白会在RSV挑战时导致肺嗜酸性粒细胞增多，而用表达融合（F）蛋白的VV免疫小鼠免疫。我们分析了对与氨基酸51至66相对应的RSV蛋白内I-E-E-D限制的CD4 T细胞表位的CD4 T细胞反应，以更好地了解G与G versus v versus v versus v versus v versus v versus v versus v versus v versus v versus的相似性F蛋白。用G蛋白进行疫苗接种可诱导RSV G特异性Th1和Th2细胞的混合物与受限制的T细胞受体库的混合物。相比之下，我们在这里证明，使用F蛋白的免疫引起了主要表现出Th1表型的RSV F特异性CD4 T细胞的广泛曲目。但是，在没有伽马干扰素（IFN-GAMMA）的情况下，RSV F51-66特异性CD4 T细胞分泌的白介素-5，而小鼠在RSV挑战后会出现肺嗜酸性粒细胞增多。与野生型对照相比，IFN-GAMMA缺陷型小鼠体重减轻降低，这表明IFN-GAMMA加剧了全身性疾病。这些数据表明，在继发性RSV感染期间，IFN-GAMMA可能具有有益和有害作用。
Secondary exposure to respiratory syncytial virus (RSV) can lead to immunopathology and enhanced disease in vaccinated individuals. Vaccination with individual RSV proteins influences the type of secondary RSV-specific immune response that develops upon challenge RSV infection, as well as the extent of immunopathology. RSV-specific memory CD4 T cells can directly contribute to immunopathology through their cytokine production. Immunization of BALB/c mice with a recombinant vaccinia virus (vv) expressing the attachment (G) protein of RSV results in pulmonary eosinophilia upon RSV challenge, whereas immunization of mice with a vv expressing the fusion (F) protein does not. We analyzed the CD4 T-cell response to an I-E-d-restricted CD4 T-cell epitope within the F protein of RSV corresponding to amino acids 51 to 66 in an effort to better understand the similarities and differences in the immune response elicited by the G versus the F protein. Vaccination with the G protein induces a mixture of RSV G-specific Th1 and Th2 cells with a restricted T-cell receptor repertoire. In contrast, we demonstrate here that immunization with the F protein elicits a broad repertoire of RSV F-specific CD4 T cells that predominantly exhibit a Th1 phenotype. However, in the absence of gamma interferon (IFN-gamma), RSV F51-66-specific CD4 T cells secreted interleukin-5, and mice developed pulmonary eosinophilia after RSV challenge. IFN-gamma-deficient mice exhibited decreased weight loss compared to wild-type controls, suggesting that IFN-gamma exacerbates systemic disease. These data demonstrate that IFN-gamma can have both beneficial and detrimental effects during a secondary RSV infection.