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

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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, 2022. "Heterogeneity and transcriptome changes of human CD8+ T cells across nine decades of life," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32869-x
    DOI: 10.1038/s41467-022-32869-x
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    References listed on IDEAS

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    2. Wright, Marvin N. & Ziegler, Andreas, 2017. "ranger: A Fast Implementation of Random Forests for High Dimensional Data in C++ and R," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 77(i01).
    3. Bates, Douglas & Mächler, Martin & Bolker, Ben & Walker, Steve, 2015. "Fitting Linear Mixed-Effects Models Using lme4," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 67(i01).
    4. Friedman, Jerome H. & Hastie, Trevor & Tibshirani, Rob, 2010. "Regularization Paths for Generalized Linear Models via Coordinate Descent," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 33(i01).
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