Developmental Regulation of Effector and Resident Memory T Cell Generation during Pediatric Viral Respiratory Tract Infection.
Developmental Regulation of Effector and Resident Memory T Cell Generation during Pediatric Viral Respiratory Tract Infection.
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DOI：
10.4049/jimmunol.1800396
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发表时间：
2018-07-15
期刊：
影响因子：
--
通讯作者：
Farber DL
中科院分区：
文献类型：
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作者：
Connors TJ;Baird JS;Yopes MC;Zens KD;Pethe K;Ravindranath TM;Ho SH;Farber DL
病毒性呼吸道感染（VRTI）仍然是婴幼儿发病和死亡的主要原因。在小鼠中，对VRTI的最佳保护是通过将效应T细胞募集到肺部和呼吸道，随后建立组织常驻记忆T细胞（Trm）来提供长期保护。在儿童VRTI中，这些T细胞募集到呼吸道的关键过程、它们在疾病发病机制中的作用以及局部保护性免疫的建立仍未明确。本研究研究了婴幼儿VRTI患者上呼吸道和下呼吸道（分别为URT和LRT）的T细胞反应，揭示了T细胞分化和Trm原位生成的发育调控。我们发现上呼吸道和下呼吸道的T细胞反应之间存在直接的一致性，包括与疾病严重程度相关的效应CD8+T细胞的优势。在婴儿VRTI期间，上呼吸道和下呼吸道中有终末分化效应细胞（Temra）的积累，在新生儿早期Trm减少，在儿童早期随着年龄的增长Temra减少，Trm的形成增加。此外，与成人T细胞相比，人类婴儿T细胞表现出转录因子T-bet的表达增加，这表明在Trm细胞中优先产生效应的机制。本文揭示的呼吸T细胞反应的发育调节对于诊断、监测和治疗生命早期关键阶段的VRTI非常重要。
Viral respiratory tract infections (VRTI) remain a leading cause of morbidity and mortality among infants and young children. In mice, optimal protection to VRTI is mediated by recruitment of effector T cells to the lungs and respiratory tract, and subsequent establishment of tissue resident memory T cells (Trm) which provide longterm protection. These critical processes of T cell recruitment to the respiratory tract, their role in disease pathogenesis, and establishment of local protective immunity remain undefined in pediatric VRTI. Here we investigated T cell responses in the upper and lower respiratory tract (URT and LRT, respectively) of infants and young children with VRTI, revealing developmental regulation of T cell differentiation and Trm generation in situ. We show a direct concurrence between T cell responses in the URT and LRT, including a preponderance of effector CD8+T cells that was associated with disease severity. During infant VRTI, there was an accumulation of terminally differentiated effector cells (Temra) in the URT and LRT with reduced Trm in the early neonatal period, with decreased Temra and increased Trm formation with age during the early years of childhood. Moreover, human infant T cells exhibit increased expression of the transcription factor T-bet compared to adult T cells, suggesting a mechanism for preferential generation of effector over Trm cells. The developmental regulation of respiratory T cell responses as revealed here is important for diagnosing, monitoring and treating VRTI in the critical early life stages.
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影响因子：
32.4
作者：
Sathaliyawala T;Kubota M;Yudanin N;Turner D;Camp P;Thome JJ;Bickham KL;Lerner H;Goldstein M;Sykes M;Kato T;Farber DL
通讯作者：
Farber DL
影响因子：
3.6
作者：
Jansen, Rogier R.;Schinkel, Janke;Pajkrt, Dasja
通讯作者：
Pajkrt, Dasja
影响因子：
82.9
作者：
Gibbons, Deena;Fleming, Paul;Hayday, Adrian
通讯作者：
Hayday, Adrian
DOI：
10.4049/jimmunol.1400553
发表时间：
2014-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Smith NL;Wissink E;Wang J;Pinello JF;Davenport MP;Grimson A;Rudd BD
通讯作者：
Rudd BD
DOI：
10.1038/nri3567
发表时间：
2014-01
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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