Heterogeneity and transcriptome changes of human CD8+ T cells across nine decades of life

Jian Lu, Raheel Ahmad, Thomas Nguyen, Jeffrey Cifello, Humza Hemani, Jiangyuan Li, Jinguo Chen, Siyi Li, Jing Wang, Achouak Achour, Joseph Chen, Meagan Colie, Ana Lustig, Christopher Dunn, Linda Zukley, Chee W. Chia, Irina Burd, Jun Zhu, Luigi Ferrucci and Nan-ping Weng ()
Additional contact information
Jian Lu: Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health
Raheel Ahmad: Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health
Thomas Nguyen: Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health
Jeffrey Cifello: Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health
Humza Hemani: Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health
Jiangyuan Li: Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health
Jinguo Chen: Center for Human Immunology, Autoimmunity and Inflammation, National Institutes of Health
Siyi Li: Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health
Jing Wang: Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health
Achouak Achour: Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health
Joseph Chen: Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health
Meagan Colie: Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health
Ana Lustig: Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health
Christopher Dunn: Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health
Linda Zukley: Translational Gerontology Branch, National Institute on Aging, National Institutes of Health
Chee W. Chia: Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health
Irina Burd: Johns Hopkins University School of Medicine
Jun Zhu: National Heart, Lung, and Blood Institute, National Institutes of Health
Luigi Ferrucci: Translational Gerontology Branch, National Institute on Aging, National Institutes of Health
Nan-ping Weng: Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract The decline of CD8+ T cell functions contributes to deteriorating health with aging, but the mechanisms that underlie this phenomenon are not well understood. We use single-cell RNA sequencing with both cross-sectional and longitudinal samples to assess how human CD8+ T cell heterogeneity and transcriptomes change over nine decades of life. Eleven subpopulations of CD8+ T cells and their dynamic changes with age are identified. Age-related changes in gene expression result from changes in the percentage of cells expressing a given transcript, quantitative changes in the transcript level, or a combination of these two. We develop a machine learning model capable of predicting the age of individual cells based on their transcriptomic features, which are closely associated with their differentiation and mutation burden. Finally, we validate this model in two separate contexts of CD8+ T cell aging: HIV infection and CAR T cell expansion in vivo.

Date: 2022
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DOI: 10.1038/s41467-022-32869-x

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