TRM integrins CD103 and CD49a differentially support adherence and motility after resolution of influenza virus infection

TRM integrins CD103 and CD49a differentially support adherence and motility after resolution of influenza virus infection
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DOI:
10.1073/pnas.1915681117
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发表时间:
2020-06-02
影响因子:
11.1
通讯作者:
Topham, David J.
Topham, David J.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Reilly, Emma C.;Emo, Kris Lambert;Topham, David J.

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组织驻留记忆 CD8 T (T-RM) 细胞是一种独特的免疫记忆子集,它在感染部位的外周组织中发育并保留,在未来再次暴露于该病原体时提供宿主抵抗力。在肺系统中,TRM 通过 S1P 拮抗剂 CD69 和整合素 CD103/β 7 和 CD49a/CD29(β 1) 的表达来识别。与 CD69 对 CD8 T 细胞的既定作用相反,CD103 和 CD49a 在该群体中的功能尚不明确。本研究检查了 CD103 和 CD49a 的表达模式和功能,特别关注它们在流感病毒感染期间对 T 细胞运动的影响。我们发现,TRM 细胞表面表型在感染后 2 周形成,大多数细胞群表达 CD49a,而一小部分细胞也表达 CD103 阳性。尽管之前已经确定了在外周组织中保留 TRM 的作用,但 CD49a 可以促进病毒特异性 CD8 T 细胞在体外和体内的运动。这些结果表明 CD49a 可能有助于 TRM 群体的局部监测机制。
Tissue-resident memory CD8 T (T-RM) cells are a unique immune memory subset that develops and remains in peripheral tissues at the site of infection, providing future host resistance upon reexposure to that pathogen. In the pulmonary system, TRM are identified through S1P antagonist CD69 and expression of integrins CD103/beta 7 and CD49a/CD29(beta 1). Contrary to the established role of CD69 on CD8 T cells, the functions of CD103 and CD49a on this population are not well defined. This study examines the expression patterns and functions of CD103 and CD49a with a specific focus on their impact on T cell motility during influenza virus infection. We show that the TRM cell surface phenotype develops by 2 wk postinfection, with the majority of the population expressing CD49a and a subset that is also positive for CD103. Despite a previously established role in retaining TRM in peripheral tissues, CD49a facilitates locomotion of virus-specific CD8 T cells, both in vitro and in vivo. These results demonstrate that CD49a may contribute to local surveillance mechanisms of the TRM population.