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Human circulating and tissue-resident memory CD8+ T cells

Nature Immunology volume 24, pages 1076–1086 (2023)Cite this article

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An Author Correction to this article was published on 17 July 2023

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Abstract

Our current knowledge of human memory CD8+ T cells is derived largely from studies of the intravascular space. However, emerging data are starting to challenge some of the dogmas based on this work, suggesting that a conceptual revision may be necessary. In this review, we provide a brief history of the field and summarize the biology of circulating and tissue-resident memory CD8+ T cells, which are ultimately responsible for effective immune surveillance. We also incorporate recent findings into a biologically integrated model of human memory CD8+ T cell differentiation. Finally, we address how future innovative human studies could improve our understanding of anatomically localized CD8+ T cells to inform the development of more effective immunotherapies and vaccines, the need for which has been emphasized by the global struggle to contain severe acute respiratory syndrome coronavirus 2.

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Fig. 1: Heterogeneity of CD8+ TEM cells.
Fig. 2: Characteristics of CD8+ TRM cells.
Fig. 3: Classification of memory CD8+ T cell subsets in humans.

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Acknowledgements

M.B. was supported by the Swedish Research Council (2018-02330, 2020-06121 and 2021-04779), the Knut and Alice Wallenberg Foundation (KAW 2021.0136), the European Research Council (101057129 and 101041484), the Karolinska Institutet (2019-00969), the Swedish Society for Medical Research (CG-22-0009), the Swedish Cancer Society (22 2237 Pj), the Åke Wibergs Stiftelse (M20-0190) and the Jonas Söderquist Stiftelse. D.A.P. was supported by the National Institute for Health Research via grant COV-LT2-0041. L.K.M. was supported by a Senior Medical Research Fellowship from the Sylvia and Charles Viertel Charitable Foundation and by a National Health and Medical Research Council Leadership Investigator Grant. M.R.B. was supported by the National Institutes of Health via grants NIAID U19-A1-149680, R21-AI172629, P01-AI31338, P30-AI045008 (Penn Center for AIDS Research), UM-1AI164570 (BEAT-HIV Collaboratory) and NIDDK UC4-DK-112217, and by the Juvenile Diabetes Research Foundation via grant SRA-2022-1237-S-B.

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Authors and Affiliations

  1. Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden

    Marcus Buggert

  2. Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK

    David A. Price

  3. Systems Immunity Research Institute, Cardiff University School of Medicine, Cardiff, UK

    David A. Price

  4. Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia

    Laura K. Mackay

  5. Institute for Immunology and Center for AIDS Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Michael R. Betts

  6. Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Michael R. Betts

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M.B., D.A.P., L.K.M. and M.R.B. participated in the writing process and contributed intellectually.

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M.B. is a consultant for Oxford Immunotec, Mabtech, Pfizer, BMS and MSD. M.R.B. is a consultant for Interius Biotherapeutics. D.A.P. and L.K.M. declare no competing interests.

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Buggert, M., Price, D.A., Mackay, L.K. et al. Human circulating and tissue-resident memory CD8+ T cells. Nat Immunol 24, 1076–1086 (2023). https://doi.org/10.1038/s41590-023-01538-6

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