Enhanced generation of influenza-specific tissue resident memory CD8 T cells in NK-depleted mice.
Enhanced generation of influenza-specific tissue resident memory CD8 T cells in NK-depleted mice.
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DOI：
10.1038/s41598-021-88268-7
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发表时间：
2021-04-26
影响因子：
4.6
通讯作者：
Klonowski KD
中科院分区：
文献类型：
--
作者：
Rose DL;Reagin KL;Oliva KE;Tompkins SM;Klonowski KD
自然杀伤 (NK) 细胞是直接接触流感和流感感染细胞的第一批效应细胞之一，它们的激活不仅影响其内在功能，还影响随后的 CD8+ T 细胞反应。我们利用 NK 细胞耗竭模型来探究 NK 细胞对抗流感 CD8+ T 细胞记忆发展的贡献。 NK 细胞消融增加了呼吸道和肺引流淋巴结中流感特异性记忆 CD8+ T 细胞的数量。有趣的是，尽管在致命的异亚型攻击后，浸润呼吸道的重新激活的 CD8+ T 细胞显着减少，但在原发性流感感染期间耗尽 NK 细胞的动物以及 NK 完整的动物一样受到保护。相反，NK 缺陷动物的保护似乎是通过在攻击后两天内快速重新激活大量肺组织驻留 (TRM) 记忆细胞来实现的。对 NK 细胞消融如何增强呼吸 TRM 的进一步询问表明，TRM 的发展独立于整体和 NK 细胞衍生的 IFN-γ。这些数据表明，接种活的非致命性流感病毒后，NK 细胞活化减少，从而增加了区室化、广泛保护性记忆 CD8+ T 细胞的生成，并降低了随后流感感染后发生 CD8+ T 细胞介导的病理学的风险。
Natural Killer (NK) cells are among the first effectors to directly contact influenza and influenza-infected cells and their activation affects not only their intrinsic functions, but also subsequent CD8+ T cell responses. We utilized a NK cell depletion model to interrogate the contribution of NK cells to the development of anti-influenza CD8+ T cell memory. NK cell ablation increased the number of influenza-specific memory CD8+ T cells in the respiratory tract and lung-draining lymph node. Interestingly, animals depleted of NK cells during primary influenza infection were protected as well as their NK-intact counterparts despite significantly fewer reactivated CD8+ T cells infiltrating the respiratory tract after lethal, heterosubtypic challenge. Instead, protection in NK-deficient animals seems to be conferred by rapid reactivation of an enlarged pool of lung tissue-resident (TRM) memory cells within two days post challenge. Further interrogation of how NK cell ablation enhances respiratory TRM indicated that TRM development is independent of global and NK cell derived IFN-γ. These data suggest that reduction in NK cell activation after vaccination with live, non-lethal influenza virus increases compartmentalized, broadly protective memory CD8+ T cell generation and decreases the risk of CD8+ T cell-mediated pathology following subsequent influenza infections.
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