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Large-Scale HLA Tetramer Tracking of T Cells during Dengue Infection Reveals Broad Acute Activation and Differentiation into Two Memory Cell Fates.
Immunity ( IF 25.5 ) Pub Date : 2019-11-19 , DOI: 10.1016/j.immuni.2019.10.007
Melissa Hui Yen Chng 1 , Mei Qiu Lim 2 , Angeline Rouers 1 , Etienne Becht 1 , Bernett Lee 1 , Paul A MacAry 3 , David Chien Lye 4 , Yee Sin Leo 5 , Jinmiao Chen 1 , Katja Fink 1 , Laura Rivino 6 , Evan W Newell 7
Immunity ( IF 25.5 ) Pub Date : 2019-11-19 , DOI: 10.1016/j.immuni.2019.10.007
Melissa Hui Yen Chng 1 , Mei Qiu Lim 2 , Angeline Rouers 1 , Etienne Becht 1 , Bernett Lee 1 , Paul A MacAry 3 , David Chien Lye 4 , Yee Sin Leo 5 , Jinmiao Chen 1 , Katja Fink 1 , Laura Rivino 6 , Evan W Newell 7
Affiliation
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T cells play important multifaceted roles during dengue infection, and understanding their responses is important for defining correlates of protective immunity and identifying effective vaccine antigens. Using mass cytometry and a highly multiplexed peptide-HLA (human leukocyte antigen) tetramer staining strategy, we probed T cells from dengue patients-a total of 430 dengue and control candidate epitopes-together with key markers of activation, trafficking, and differentiation. During acute disease, dengue-specific CD8+ T cells expressed a distinct profile of activation and trafficking receptors that distinguished them from non-dengue-specific T cells. During convalescence, dengue-specific T cells differentiated into two major cell fates, CD57+ CD127--resembling terminally differentiated senescent memory cells and CD127+ CD57--resembling proliferation-capable memory cells. Validation in an independent cohort showed that these subsets remained at elevated frequencies up to one year after infection. These analyses aid our understanding of the generation of T cell memory in dengue infection or vaccination.
中文翻译：
登革热感染期间T细胞的大规模HLA四聚体追踪揭示了广泛的急性激活和分化为两种记忆细胞的命运。
T细胞在登革热感染过程中起着重要的多方面作用，了解它们的反应对于定义保护性免疫的相关性和鉴定有效的疫苗抗原非常重要。使用大规模流式细胞仪和高度复用的肽-HLA（人类白细胞抗原）四聚体染色策略，我们检测了登革热患者的T细胞-总共430个登革热和对照候选表位-以及激活，运输和分化的关键标志物。在急性疾病期间，登革热特异性CD8 + T细胞表达出独特的激活和转运受体特征，从而将它们与非登革热特异性T细胞区分开来。在恢复期，登革热特异性T细胞分化为两个主要的细胞命运，CD57 + CD127-类似于终末分化的衰老记忆细胞，而CD127 + CD57-类似于具有增殖能力的记忆细胞。在一个独立的队列中进行的验证显示，这些亚群在感染后长达一年的时间仍保持较高的频率。这些分析有助于我们了解登革热感染或疫苗接种中T细胞记忆的产生。
更新日期：2019-11-20
中文翻译：
登革热感染期间T细胞的大规模HLA四聚体追踪揭示了广泛的急性激活和分化为两种记忆细胞的命运。
T细胞在登革热感染过程中起着重要的多方面作用，了解它们的反应对于定义保护性免疫的相关性和鉴定有效的疫苗抗原非常重要。使用大规模流式细胞仪和高度复用的肽-HLA（人类白细胞抗原）四聚体染色策略，我们检测了登革热患者的T细胞-总共430个登革热和对照候选表位-以及激活，运输和分化的关键标志物。在急性疾病期间，登革热特异性CD8 + T细胞表达出独特的激活和转运受体特征，从而将它们与非登革热特异性T细胞区分开来。在恢复期，登革热特异性T细胞分化为两个主要的细胞命运，CD57 + CD127-类似于终末分化的衰老记忆细胞，而CD127 + CD57-类似于具有增殖能力的记忆细胞。在一个独立的队列中进行的验证显示，这些亚群在感染后长达一年的时间仍保持较高的频率。这些分析有助于我们了解登革热感染或疫苗接种中T细胞记忆的产生。
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