Tissue-Resident Memory T Cells in the Lungs Protect against Acute Respiratory Syncytial Virus Infection.
Tissue-Resident Memory T Cells in the Lungs Protect against Acute Respiratory Syncytial Virus Infection.
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DOI：
10.4049/immunohorizons.2000067
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发表时间：
2021-02-03
期刊：
影响因子：
--
通讯作者：
Varga SM
中科院分区：
文献类型：
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作者：
Luangrath MA;Schmidt ME;Hartwig SM;Varga SM
呼吸道合胞病毒（RSV）是幼儿下呼吸道感染的主要原因。T细胞反应在促进清除急性RSV感染中起关键作用，记忆T细胞反应对于防止继发性RSV暴露至关重要。组织常驻记忆（TRM） T细胞已被确定为记忆T细胞的一个亚群，它驻留在非淋巴组织中，对提供长期免疫至关重要。关于急性RSV感染后引起的TRM T细胞反应的建立和持续时间，以及它们在防止重复RSV感染中的作用，目前的信息有限。在这里，我们检测了急性RSV感染后BALB/c小鼠肺中TRM CD4和CD8 T细胞的大小、表型和保护能力。在RSV感染后149天，肺内建立了TRM CD4和CD8 T细胞并减弱。为了确定TRMs的保护能力，在用表达rsv衍生的CD4或CD8 T细胞表位的重组流感病毒攻击rsv免疫小鼠之前，使用FTY-720给药来阻止外周记忆T细胞进入肺部。我们在RSV免疫小鼠中观察到增强的病毒清除率，这表明TRM CD8 T细胞有助于防止继发性RSV感染。鉴于trm的保护能力，未来的RSV候选疫苗应侧重于在肺内产生这些细胞群，以诱导对RSV感染的有效免疫。
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in young children. The T cell response plays a critical role in facilitating clearance of an acute RSV infection, and memory T cell responses are vital for protection against secondary RSV exposures. Tissue resident memory (TRM) T cells have been identified as a subset of memory T cells that reside in non-lymphoid tissues and are critical for providing long-term immunity. There is currently limited information regarding the establishment and longevity of TRM T cell responses elicited following an acute RSV infection as well as their role in protection against repeated RSV infections. Here we examined the magnitude, phenotype, and protective capacity of TRM CD4 and CD8 T cells in the lungs of BALB/c mice following an acute RSV infection. TRM CD4 and CD8 T cells were established within the lungs and waned by 149 days following RSV infection. To determine the protective capacity of TRMs, FTY-720 administration was used to prevent trafficking of peripheral memory T cells into the lungs prior to challenge of RSV-immune mice with a recombinant influenza virus expressing either an RSV-derived CD4 or CD8 T cell epitope. We observed enhanced viral clearance in RSV-immune mice suggesting that TRM CD8 T cells can contribute to protection against a secondary RSV infection. Given the protective capacity of TRMs, future RSV vaccine candidates should focus on the generation of these cell populations within the lung to induce effective immunity against RSV infection.