Protective influenza-specific CD8 T cell responses require interactions with dendritic cells in the lungs.
Protective influenza-specific CD8 T cell responses require interactions with dendritic cells in the lungs.
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DOI：
10.1084/jem.20080314
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发表时间：
2008-07-07
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
流感感染诱导快速但短暂的树突状细胞（DC）从肺迁移到淋巴结（LN），随后DC大量募集到肺中而随后不迁移到LN。鉴于外周DC主要被认为参与迁移到淋巴组织后的适应性免疫的启动，这些新肺募集的DC在流感病毒免疫中起什么作用尚不清楚。在这项研究中，我们证明了非LN迁移性肺DC亚群的丢失增加了死亡率，维持了较高的病毒滴度，并损害了肺CD8 T细胞反应。用肺浆细胞样DC、CD8α+ DC或间质性DC重建肺以细胞接触、主要组织相容性复合物I和流感肽依赖性方式恢复CD8 T细胞应答。因此，在LN中初始活化后，保护性流感特异性CD8 T细胞应答需要额外的抗原依赖性相互作用，特别是与肺中的DC。
Influenza infections induce a rapid, but transient, dendritic cell (DC) migration from the lungs to the lymph nodes (LNs) that is followed by substantial recruitment of DCs into the lungs without subsequent migration to the LNs. Given that peripheral DCs are primarily thought to be involved in the initiation of adaptive immunity after migration into lymphoid tissues, what role these newly lung-recruited DCs play in influenza virus immunity is unclear. In this study, we demonstrate that loss of non-LN migratory pulmonary DC subsets increases mortality, sustains higher viral titers, and impairs pulmonary CD8 T cell responses. Reconstitution of the lungs with pulmonary plasmacytoid DCs, CD8α+ DCs, or interstitial DCs restores CD8 T cell responses in a cell contact–, major histocompatability complex I–, and influenza peptide–dependent manner. Thus, after their initial activation in the LN, protective influenza-specific CD8 T cell responses require additional antigen-dependent interactions, specifically with DCs in the lungs.
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