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

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

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish
Pages (from-to)2836-2854.e9
JournalImmunity
Volume56
Issue number12
DOIs
StatePublished - Dec 12 2023

Keywords

  • CCR4CD8 T cells
  • NKG2CGZMBCD8 T cells
  • PBMC
  • TCR/BCR sequencing
  • Th2
  • aging
  • human
  • scRNA-seq
  • surface protein

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