美国华盛顿大学医学院Maxim N. Artyomov团队绘制健康人类血液的单细胞图谱，揭示了与衰老相关的NKG2C+GZMB−CD8+记忆T细胞的减少和类型2记忆T细胞的积累。这一研究成果发表在2023年11月13日出版的国际学术期刊《免疫》上。

他们使用单细胞RNA/T细胞受体(TCR)/BCR-seq与蛋白质特征条形码，分析了来自166名25-85岁健康个体的317份样本。由此，他们生成了一个来自约200万个细胞的数据集，描述了55个血液免疫细胞亚群。12个亚群随年龄变化，包括GZMK+CD8+ T细胞和HLA-DR+CD4+ T细胞的积累。与其他T细胞记忆亚群相反，转录上差异的NKG2C+GZMB - CD8+ T细胞出乎意料的随着年龄的增长而下降。

此外，他们发现CD4+和CD8+ T细胞区室(CCR4+CD8+ Tcm和Th2 CD4+ Tmem)中表达2型/白细胞介素(IL)4的记忆亚群与衰老相关的增加，表明免疫稳态随着年龄的增长而发生系统性的功能变化。他们的工作为健康人类衰老提供了新的见解和全面注释的资源。

据介绍，对不同年龄的健康人类血液进行广泛、大规模的单细胞分析是建立一个系统理解人类衰老的框架所需要的关键任务之一。

附：英文原文

Title: Single-cell atlas of healthy human blood unveils age-related loss of NKG2C+GZMBCD8+ memory T cells and accumulation of type 2 memory T cells

Author: Marina Terekhova, Amanda Swain, Pavla Bohacova, Ekaterina Aladyeva, Laura Arthur, Anwesha Laha, Denis A. Mogilenko, Samantha Burdess, Vladimir Sukhov, Denis Kleverov, Barbora Echalar, Petr Tsurinov, Roman Chernyatchik, Kamila Husarcikova, Maxim N. Artyomov

Issue&Volume: 2023-11-13

Abstract: Extensive, large-scale single-cell profiling of healthy human blood at different ages is one of the critical pending tasks required to establish a framework for the systematic understanding of human aging. Here, using single-cell RNA/T cell receptor (TCR)/BCR-seq with protein feature barcoding, we profiled 317 samples from 166 healthy individuals aged 25–85 years old. From this, we generated a dataset from ～2 million cells that described 55 subpopulations of blood immune cells. Twelve subpopulations changed with age, including the accumulation of GZMK+CD8+ T cells and HLA-DR+CD4+ T cells. In contrast to other T cell memory subsets, transcriptionally distinct NKG2C+GZMBCD8+ T cells counterintuitively decreased with age. Furthermore, we found a concerted age-associated increase in type 2/interleukin (IL)4-expressing memory subpopulations across CD4+ and CD8+ T cell compartments (CCR4+CD8+ Tcm and Th2 CD4+ Tmem), suggesting a systematic functional shift in immune homeostasis with age. Our work provides novel insights into healthy human aging and a comprehensive annotated resource.

DOI: 10.1016/j.immuni.2023.10.013

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00453-3