IL-15 trans-presentation by pulmonary dendritic cells promotes effector CD8 T cell survival during influenza virus infection.
IL-15 trans-presentation by pulmonary dendritic cells promotes effector CD8 T cell survival during influenza virus infection.
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DOI：
10.1084/jem.20091711
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发表时间：
2010-03-15
期刊：
影响因子：
--
通讯作者：
Legge KL
中科院分区：
文献类型：
--
作者：
McGill J;Van Rooijen N;Legge KL
我们最近证实，在流感病毒感染后，外周CD8T细胞需要两次单独的激活击打才能在肺内积聚到高数量：第一次与淋巴结中成熟的、携带抗原的树突状细胞(DC)相互作用，第二次与肺部MHC I病毒抗原携带的肺树突状细胞(DC)相互作用。我们证明，在没有肺常驻DC亚群的情况下，病毒特异性CD8T细胞在肺中的凋亡水平显著增加；然而，与肺浆细胞样树突状细胞和CD8CD8α+树突状细胞重建促进了T细胞在肺中的存活和积累。此外，我们的结果表明，流感病毒感染后DC的缺失导致肺中IL-15水平显著降低，并且肺DC介导的肺内病毒特异性CD8T细胞应答需要通过DC表达的IL-15Rα反式递呈IL-15。本研究证明了DC反式呈递的IL-15在病毒感染后促进效应CD8 T细胞存活方面的一个关键的、新的要求，并提示这种反式呈递可能成为发展独特的抗病毒治疗和更有效的疫苗策略的重要靶点。
We have recently demonstrated that peripheral CD8 T cells require two separate activation hits to accumulate to high numbers in the lungs after influenza virus infection: a primary interaction with mature, antigen-bearing dendritic cells (DCs) in the lymph node, and a second, previously unrecognized interaction with MHC I–viral antigen–bearing pulmonary DCs in the lungs. We demonstrate that in the absence of lung-resident DC subsets, virus-specific CD8 T cells undergo significantly increased levels of apoptosis in the lungs; however, reconstitution with pulmonary plasmacytoid DCs and CD8α+ DCs promotes increased T cell survival and accumulation in the lungs. Further, our results show that the absence of DCs after influenza virus infection results in significantly reduced levels of IL-15 in the lungs and that pulmonary DC–mediated rescue of virus-specific CD8 T cell responses in the lungs requires trans-presentation of IL-15 via DC-expressed IL-15Rα. This study demonstrates a key, novel requirement for DC trans-presented IL-15 in promoting effector CD8 T cell survival in the respiratory tract after virus infection, and suggests that this trans-presentation could be an important target for the development of unique antiviral therapies and more effective vaccine strategies.
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DOI：
10.1084/jem.20021910
发表时间：
2003-05-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
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影响因子：
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DOI：
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发表时间：
2005-09-05
期刊：
The Journal of experimental medicine
影响因子：
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