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The who's who of T ‐cell differentiation: Human memory T ‐cell subsets
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Following antigen encounter and subsequent resolution of the immune response, a single naïve T cell is able to generate multiple subsets of memory T cells with different phenotypic and functional properties and gene expression profiles. Single‐cell technologies, first and foremost flow cytometry, have revealed the complex heterogeneity of the memory T ‐cell compartment and its organization into subsets. However, a consensus has still to be reached, both at the semantic (nomenclature) and phenotypic level, regarding the identification of these subsets. Here, we review recent developments in the characterization of the heterogeneity of the memory T ‐cell compartment, and propose a unified classification of both human and nonhuman primate T cells on the basis of phenotypic traits and in vivo properties. Given that vaccine studies and adoptive cell transfer immunotherapy protocols are influenced by these recent findings, it is important to use uniform methods for identifying and discussing functionally distinct subsets of T cells.
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“Multidimensional flow cytometry with up to 40 parameters enables a deeper phenotyping and characterization of the immune system, which is required as cellular subsets require more and more markers for accurate definition [81].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [81]
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“Moreover, by tSNE, we confirmed that TCMs further differentiated into transitional memory T cells (TTMs) in vitro during viral outgrowth (Figures 4C and 4D) as a logical consequence after stimulation.”
From Revealing viral and cellular dynamics of HIV-1 at the single-cell level during early treatment periods (2023) · cites this paper as [51]
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“The patient showed increased number of CD8 + T cells, which showed a more activated and differentiated phenotype as indicated by an elevated proportion of HLA-DR + or CD38 + cells (7).”
From A Novel Homozygous RHOH Variant Associated with T Cell Dysfunction and Recurrent Opportunistic Infections (2024) · cites this paper as [7]
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“a small population of memory T cells endowed with elevated proliferative and self-renewal capacities has been identified within the CD45RA+CCR7+ naïve T-cell gate. These cells have been termed stem cell-like memory (Tscm) cells [140] and can be distinguished from truly naïve T cells based on the expression of the FAS receptor (CD95) (Figure 8A) [81].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [81]
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“Both the CD4 + and CD8 + T-cell subsets displayed a signi cantly lower proportion of CD28 + cells, suggesting a decrease in naïve T cell which express a high level of differentiation marker CD28 (7).”
From A Novel Homozygous RHOH Variant Associated with T Cell Dysfunction and Recurrent Opportunistic Infections (2024) · cites this paper as [7]
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“In agreement with the naive and/or CM state of T cells in these clusters, high expression of IL-7 receptor IL7R (CD127) was also detected (Mahnke et al., 2013).”
BackgroundDe Biasi, S., Meschiari, M., Gibellini, L., Bellinazzi, C., Borella, R., Fidanza, L., Gozzi, L., Iannone, A., Lo Tartaro, D., Mattioli, M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17292-4 · Cited by 789
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“It is known that both naïve and memory T cells express CCR7 and SELL genes, which are required for lymph node migration, whereas these genes are not expressed in effector T cells 36,37 .”
Background
Metadata
- Authors
- Mahnke, Y. D., Brodie, T. M., Sallusto, F., Roederer, M., & Lugli, E.
- Affiliations
- University of Pennsylvania (US)
- Institute for Research in Biomedicine (CH)
- National Institutes of Health (US)
- Humanitas University (IT)
- Corresponding author
- Roederer, Mario
- Lugli, Enrico
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 2013-10-30
- Volume
- 43
- Issue
- 11
- Pages
- 2797-2809
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- OpenAlex
- W1572743872
- Cited by
- 817
- References
- 113
- Citations by year
- 2026: 25 · 2025: 42 · 2024: 64 · 2023: 76 · 2022: 100 · 2021: 93 · 2020: 105 · 2019: 81 · 2018: 71 · 2017: 53 · 2016: 37 · 2015: 39 · 2014: 28 · 2013: 1
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
- Funders
- National Science Foundation
- European Commission (241745, 322093)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (131092)
- Fondazione Cariplo (2012-0683)
- Associazione Italiana per la Ricerca sul Cancro
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases
- FP7 Health
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- memory T cells, T cell differentiation, T cell memory subsets, T cell heterogeneity, T cell phenotype, vaccine immunology, adoptive cell transfer, single-cell technologies
- MeSH terms
- Cell Differentiation, Humans, Immunologic Memory, Lymphocyte Activation, Gene Expression, T-Lymphocyte Subsets, Immunotherapy, Adoptive, Adoptive Transfer
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