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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Change history
17 July 2023
A Correction to this paper has been published: https://doi.org/10.1038/s41590-023-01586-y
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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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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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DOI: https://doi.org/10.1038/s41590-023-01538-6