新加坡科学技术研究局Evan W. Newell和杜克-新加坡国立大学医学院Laura Rivino研究组合作发现，登革热感染期间对T细胞的大规模HLA四聚体追踪显示，T细胞广泛急性激活，并分化为两种记忆细胞。这一研究成果11月19日在线发表在《免疫》上。

他们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，检测了来自登革热患者的T细胞（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细胞表达出独特的活化和转运受体特征，从而将它们与非登革热特异性T细胞区分开来。

在恢复过程中，登革热特异性T细胞分化为两个主要的细胞命运，即CD57 + CD127-类似的终末分化衰老记忆细胞和CD127 + CD57-类似增殖的记忆细胞。在一个独立的实验中进行的验证表明，这些亚群在感染后长达一年的时间仍保持较高的频率。这些分析有助于了解登革热感染或疫苗接种中T细胞记忆的产生。

据悉，T细胞在登革热感染过程中起着重要的多方面作用，了解它们的免疫应答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。

附：英文原文

Title: Large-Scale HLA Tetramer Tracking of T Cells during Dengue Infection Reveals Broad Acute Activation and Differentiation into Two Memory Cell Fates

Author: Melissa Hui Yen Chng, Mei Qiu Lim, Angeline Rouers, Etienne Becht, Bernett Lee, Paul A. MacAry, David Chien Lye, Yee Sin Leo, Jinmiao Chen, Katja Fink, Laura Rivino, Evan W. Newell

Issue&Volume: November 19, 2019

Abstract: T cells play important multifaceted roles during dengue infection, and understandingtheir responses is important for defining correlates of protective immunity and identifyingeffective vaccine antigens. Using mass cytometry and a highly multiplexed peptide-HLA(human leukocyte antigen) tetramer staining strategy, we probed T cells from denguepatients—a total of 430 dengue and control candidate epitopes—together with key markersof activation, trafficking, and differentiation. During acute disease, dengue-specificCD8+ T cells expressed a distinct profile of activation and trafficking receptors that distinguishedthem from non-dengue-specific T cells. During convalescence, dengue-specific T cellsdifferentiated 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 cohortshowed 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 dengueinfection or vaccination.

DOI: 10.1016/j.immuni.2019.10.007

Source: https://www.cell.com/immunity/fulltext/S1074-7613(19)30451-0