A Distinct Lung-Interstitium-Resident Memory CD8(+) T Cell Subset Confers Enhanced Protection to Lower Respiratory Tract Infection.

A Distinct Lung-Interstitium-Resident Memory CD8(+) T Cell Subset Confers Enhanced Protection to Lower Respiratory Tract Infection.
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独特的肺部 - 居民居民记忆CD8(+)T细胞子集赋予了对下呼吸道感染的增强保护。

DOI:
10.1016/j.celrep.2016.07.037
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发表时间:
2016-08-16
期刊:
影响因子:
8.8
通讯作者:
Joyce S
Joyce S
中科院分区:
生物学1区
文献类型:
--
作者:
Gilchuk P;Hill TM;Guy C;McMaster SR;Boyd KL;Rabacal WA;Lu P;Shyr Y;Kohlmeier JE;Sebzda E;Green DR;Joyce S

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鼻腔接种诱导的保护性记忆CD8+T细胞亚群的性质和解剖位置仍然知之甚少。我们开发了一种疫苗接种模型,以评估保护性记忆CD8+T细胞的解剖位置及其在下呼吸道感染中的作用。以非复制型CD8+T细胞为靶向抗原的基因工程疫苗局部鼻腔免疫,而不是全身免疫,可增强对致死性呼吸道病毒攻击的保护作用。这种保护依赖于一种独特的CXCR3LO常驻记忆CD8+T细胞(Trm)群体,该群体优先定位于肺间质。间质Trm-通过靠近感染发生的黏膜-在炎症可以将循环中的CD8+T细胞招募到肺组织之前采取行动。这导致最早在感染后一天就产生局部保护性免疫反应。因此,诱导肺间质Trm的疫苗策略可能对呼吸道病原体具有更好的保护作用。
The nature and anatomic location of the protective memory CD8+ T cell subset induced by intranasal vaccination remain poorly understood. We developed a vaccination model to assess the anatomic location of protective memory CD8+ T cells and their role in lower airway infections. Memory CD8+ T cells elicited by local intranasal, but not systemic vaccination with an engineered non-replicative CD8+ T cell-targeted antigen confer enhanced protection to a lethal respiratory viral challenge. This protection depends on a distinct CXCR3LO resident memory CD8+ T cell (Trm) population that preferentially localizes to the pulmonary interstitium. Interstitial Trm —by being positioned close to the mucosa where infection occurs—act before inflammation can recruit circulating memory CD8+ T cells into the lung tissue. This results in a local protective immune response as early as one day post-infection. Hence, vaccine strategies that induce lung interstitial Trm may confer better protection against respiratory pathogens
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