The number of respiratory syncytial virus (RSV)-specific memory CD8 T cells in the lung is critical for their ability to inhibit RSV vaccine-enhanced pulmonary eosinophilia.

The number of respiratory syncytial virus (RSV)-specific memory CD8 T cells in the lung is critical for their ability to inhibit RSV vaccine-enhanced pulmonary eosinophilia.
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肺中呼吸综合病毒(RSV)特异性记忆CD8 T细胞的数量对于它们抑制RSV疫苗增强肺嗜酸性嗜酸性嗜酸性嗜酸性嗜酸性嗜酸性的能力至关重要。

DOI:
10.4049/jimmunol.181.11.7958
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发表时间:
2008-12-01
影响因子:
4.4
通讯作者:
Varga, Steven M.
Varga, Steven M.
中科院分区:
医学2区
文献类型:
--
作者:
Olson, Matthew R.;Hartwig, Stacey M.;Varga, Steven M.

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接种福尔马林灭活呼吸道合胞病毒(FI-RSV)疫苗的儿童在感染自然RSV感染后出现呼吸道疾病增强,包括肺嗜酸性粒细胞增多症。可以在用FI-RSV或用表达RSV附着(G)蛋白的重组牛痘病毒(vacv)免疫的BALB/c小鼠中模拟RSV疫苗增强的疾病。我们最近证明,针对RSV免疫显性M282−90表位的记忆CD 8 T细胞通过减少RSV攻击后肺中Th 2细胞的总数,抑制vacvG或FI-RSV免疫小鼠中肺嗜酸性粒细胞增多症的发生。在这里,我们表明,记忆CD 8 T细胞特异性的RSV融合蛋白(F)内的亚显性表位不能抑制RSV攻击后,肺嗜酸性粒细胞增多症的发展,小鼠先前共免疫与vacvF和vacvG或FI-RSV。我们观察到,RSV F85特异性记忆CD 8 T细胞不能抑制肺嗜酸性粒细胞增多症的发展主要是由于RSV攻击后早期肺中F85特异性记忆CD 8 T细胞的总数不足。免疫后增加F85特异性记忆CD 8 T细胞的数量赠款它们抑制RSV疫苗增强的肺嗜酸性粒细胞增多的能力。此外,我们证明,RSV特异性记忆CD 8 T细胞,当存在足够的数量,抑制生产的Th 2相关的趋化因子CCL 17和CCL 22。综上所述,这些结果表明,RSV特异性记忆CD 8 T细胞可能会改变运输的Th 2细胞和嗜酸性粒细胞进入肺。
Children that were administered a formalin-inactivated respiratory syncytial virus (FI-RSV) vaccine experienced enhanced respiratory disease, including pulmonary eosinophilia, after contracting a natural RSV infection. RSV vaccine-enhanced disease can be mimicked in BALB/c mice immunized with either FI-RSV or with a recombinant vaccinia virus (vacv) expressing the RSV attachment (G) protein. We have recently demonstrated that memory CD8 T cells directed against the RSV immunodominant M282−90 epitope inhibit the development of pulmonary eosinophilia in either vacvG- or FI-RSV-immunized mice by reducing the total number of Th2 cells in the lung after RSV challenge. Here we show that memory CD8 T cells specific to a subdominant epitope within the RSV fusion (F) protein fail to inhibit the development of pulmonary eosinophilia after RSV challenge of mice previously co-immunized with vacvF and with either vacvG or FI-RSV. We observed that the inability of RSV F85-specific memory CD8 T cells to inhibit the development of pulmonary eosinophilia was largely due to an inadequate total number of F85-specific memory CD8 T cells in the lung at early times after RSV challenge. Increasing the number of F85-specific memory CD8 T cells after immunization grants them the ability to inhibit RSV vaccine-enhanced pulmonary eosinophilia. Moreover, we demonstrate that RSV-specific memory CD8 T cells, when present in sufficient numbers, inhibit the production of the Th2-associated chemokines CCL17 and CCL22. Taken together, these results indicate that RSV-specific memory CD8 T cells may alter the trafficking of Th2 cells and eosinophils into the lung.
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发表时间: 2000-01-17
期刊: The Journal of experimental medicine
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