Single-cell atlas of healthy human blood unveils age-related loss of NKG2C+GZMB-CD8+ memory T cells and accumulation of type 2 memory T cells 2572

Abstract Description Terekhova M1,5, Swain A1,5, Bohacova P1,5, Aladyeva E1, Arthur L1, Laha A1, Mogilenko DA1,2, Burdess S1, Sukhov V1,3, Kleverov D1,3, Echalar B1, Tsurinov P1,4, Chernyatchik R1,4, Husarcikova K1, Artyomov MN1. 1Washington University School of Medicine, 2Vanderbilt University Medical Center, 3ITMO University, 4JetBrains Research, 5Contributed equally. 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+GZMB-CD8+ 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. Funding Sources Aging Biology Foundation Topic Categories Computational and Systems Immunology (COMP)