Large-Scale HLA Tetramer Tracking of T Cells during Dengue Infection Reveals Broad Acute Activation and Differentiation into Two Memory Cell Fates
Large-Scale HLA Tetramer Tracking of T Cells during Dengue Infection Reveals Broad Acute Activation and Differentiation into Two Memory Cell Fates
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DOI：
10.1016/j.immuni.2019.10.007
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发表时间：
2019-12-17
期刊：
影响因子：
32.4
通讯作者：
Newell, Evan W.
中科院分区：
文献类型：
--
作者：
Chng, Melissa Hui Yen;Lim, Mei Qiu;Newell, Evan W.
T细胞在登革热感染过程中发挥着重要的多方面作用，了解它们的反应对于确定保护性免疫的相关性和识别有效的疫苗抗原非常重要。使用大规模细胞计数和高度多重肽HLA（人类白细胞抗原）四聚体染色策略，我们探测登革热患者的T细胞-共430登革热和对照候选表位-连同活化，贩运和分化的关键标志物。在急性疾病期间，登革热特异性CD 8（+）T细胞表达了一种独特的激活和运输受体谱，将其与非登革热特异性T细胞区分开来。在恢复期，登革特异性T细胞分化为两种主要的细胞命运，CD 57（+）CD 127（-）-类似终末分化的衰老记忆细胞和CD 127（+）CD 57（-）-类似增殖能力的记忆细胞。在一个独立的队列验证表明，这些子集保持在感染后一年的高频率。这些分析有助于我们理解登革热感染或疫苗接种中T细胞记忆的产生。
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.