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Two subsets of stem-like CD8+ memory T cell progenitors with distinct fate commitments in humans
Open accessAbstract
T cell memory relies on the generation of antigen-specific progenitors with stem-like properties. However, the identity of these progenitors has remained unclear, precluding a full understanding of the differentiation trajectories that underpin the heterogeneity of antigen-experienced T cells. We used a systematic approach guided by single-cell RNA-sequencing data to map the organizational structure of the human CD8+ memory T cell pool under physiological conditions. We identified two previously unrecognized subsets of clonally, epigenetically, functionally, phenotypically and transcriptionally distinct stem-like CD8+ memory T cells. Progenitors lacking the inhibitory receptors programmed death-1 (PD-1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) were committed to a functional lineage, whereas progenitors expressing PD-1 and TIGIT were committed to a dysfunctional, exhausted-like lineage. Collectively, these data reveal the existence of parallel differentiation programs in the human CD8+ memory T cell pool, with potentially broad implications for the development of immunotherapies and vaccines.
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“The gating strategy shown in this section is applicable for analysis of conventional αβ CD8+ T cells in any kind of physiological or clinical setting [207, 208, 222].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [208]
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Metadata
- Authors
- Galletti, G., De Simone, G., Mazza, E. M. C., Puccio, S., Mezzanotte, C., Bi, T. M., Davydov, A. N., Metsger, M., Scamardella, E., Alvisi, G., De Paoli, F., Zanon, V., Scarpa, A., Camisa, B., Colombo, F. S., Anselmo, A., Peano, C., Polletti, S., Mavilio, D., Gattinoni, L., Boi, S. K., Youngblood, B. A., Jones, R. E., Baird, D. M., Gostick, E., Llewellyn-Lacey, S., Ladell, K., Price, D. A., Chudakov, D. M., Newell, E. W., Casucci, M., & Lugli, E.
- Affiliations
- IRCCS Humanitas Research Hospital (IT)
- IRCCS Ospedale San Raffaele (IT)
- Fred Hutch Cancer Center (US)
- Central European Institute of Technology (CZ)
- National Research Council (IT)
- Humanitas University (IT)
- University of Milan (IT)
- National Institutes of Health (US)
- St. Jude Children's Research Hospital (US)
- Cardiff University (GB)
- Skolkovo Institute of Science and Technology (RU)
- Corresponding author
- Lugli, Enrico
- ORCID
- Galletti, Giovanni
- Mazza, Emilia M. C.
- Puccio, Simone
- Bi, Timothy M.
- Davydov, Alexey N.
- Metsger, Maria
- Alvisi, Giorgia
- Zanon, Veronica
- Scarpa, Alice
- Camisa, Barbara
- Colombo, Federico S.
- Anselmo, Achille
- Peano, Clelia
- Polletti, Sara
- Mavilio, Domenico
- Gattinoni, Luca
- Boi, Shannon K.
- Youngblood, Benjamin A.
- Baird, Duncan M.
- Ladell, Kristin
- Price, David A.
- Chudakov, Dmitriy M.
- Newell, Evan W.
- Casucci, Monica
- Lugli, Enrico
- Venue
- Nature Immunology
- Published
- 2020-10-12
- Volume
- 21
- Issue
- 12
- Pages
- 1552-1562
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC7610790
- OpenAlex
- W3092341078
- Cited by
- 299
- References
- 74
- Citations by year
- 2026: 31 · 2025: 49 · 2024: 66 · 2023: 53 · 2022: 51 · 2021: 46 · 2020: 3
- FWCI
- 13.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion)
- Funders
- Wellcome Trust (100326, 100326/Z/12/Z)
- Cancer Research UK (C17199/A18246/A29202, 29202, 18246)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- memory CD8+ T cells, T cell exhaustion, PD-1, TIGIT, T cell differentiation, inhibitory receptors, single-cell RNA sequencing
- MeSH terms
- Animals, Cell Differentiation, Humans, Immunologic Memory, Biomarkers, Immunophenotyping, T-Lymphocyte Subsets, CD8-Positive T-Lymphocytes, Computational Biology, Gene Expression Profiling, Mice, Lymphoid Progenitor Cells, High-Throughput Nucleotide Sequencing, Telomere Homeostasis
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