A human memory T cell subset with stem cell–like properties
Open accessAbstract
Immunological memory is thought to depend on a stem cell-like, self-renewing population of lymphocytes capable of differentiating into effector cells in response to antigen re-exposure. Here we describe a long-lived human memory T cell population that has an enhanced capacity for self-renewal and a multipotent ability to derive central memory, effector memory and effector T cells. These cells, specific to multiple viral and self-tumor antigens, were found within a CD45RO(-), CCR7(+), CD45RA(+), CD62L(+), CD27(+), CD28(+) and IL-7Rα(+) T cell compartment characteristic of naive T cells. However, they expressed large amounts of CD95, IL-2Rβ, CXCR3, and LFA-1, and showed numerous functional attributes distinctive of memory cells. Compared with known memory populations, these lymphocytes had increased proliferative capacity and more efficiently reconstituted immunodeficient hosts, and they mediated superior antitumor responses in a humanized mouse model. The identification of a human stem cell-like memory T cell population is of direct relevance to the design of vaccines and T cell therapies.
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A small population of memory T cells with elevated proliferative and self-renewal capacities has been identified within the CD45RA+CCR7+ naïve T-cell gate; these are stem cell-like memory (Tscm) cells and can be distinguished from truly naïve T cells based on FAS receptor (CD95) expression.
“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 [140]
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Self-citation
- Authors
- Gattinoni, L., Lugli, E., Ji, Y., Pos, Z., Paulos, C. M., Quigley, M. F., Almeida, J. R., Gostick, E., Yu, Z., Carpenito, C., Wang, E., Douek, D. C., Price, D. A., June, C. H., Marincola, F. M., Roederer, M., & Restifo, N. P.
- Affiliations
- National Institutes of Health (US)
- Abramson Cancer Center (US)
- Corresponding author
- Gattinoni, Luca
- Restifo, Nicholas P
- ORCID
- Venue
- Nature Medicine
- Published
- 2011-09-18
- Volume
- 17
- Issue
- 10
- Pages
- 1290-1297
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC3192229
- OpenAlex
- W2144796561
- Cited by
- 1,974
- References
- 59
- Citations by year
- 2026: 119 · 2025: 133 · 2024: 141 · 2023: 166 · 2022: 158 · 2021: 175 · 2020: 170 · 2019: 133 · 2018: 150 · 2017: 109 · 2016: 115 · 2015: 133 · 2014: 103 · 2013: 85 · 2012: 75
- FWCI
- 38.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (ZIABC010763)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- memory T cells, self-renewal, multipotency, naive T cells, immunological memory, Fas, IL-2 receptor beta, CXCR3, LFA-1, antitumor immunity, humanized mice, T cell therapy, vaccine design
- MeSH terms
- Analysis of Variance, Animals, Flow Cytometry, Humans, Immunologic Memory, T-Lymphocytes, T-Lymphocyte Subsets, Leukocyte Common Antigens, CD28 Antigens, Tumor Necrosis Factor Receptor Superfamily, Member 7, L-Selectin, Receptors, Interleukin-7, Gene Expression Profiling, Cell Proliferation, Mice, Receptors, CCR7
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