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Serial Transfer of Single-Cell-Derived Immunocompetence Reveals Stemness of CD8+ Central Memory T Cells
Open accessAbstract
Maintenance of immunological memory has been proposed to rely on stem-cell-like lymphocytes. However, data supporting this hypothesis are focused on the developmental potential of lymphocyte populations and are thus insufficient to establish the functional hallmarks of stemness. Here, we investigated self-renewal capacity and multipotency of individual memory lymphocytes by in vivo fate mapping of CD8(+) T cells and their descendants across three generations of serial single-cell adoptive transfer and infection-driven re-expansion. We found that immune responses derived from single naive T (Tn) cells, single primary, and single secondary central memory T (Tcm) cells reached similar size and phenotypic diversity, were subjected to comparable stochastic variation, and could ultimately reconstitute immunocompetence against an otherwise lethal infection with the bacterial pathogen Listeria monocytogenes. These observations establish that adult tissue stem cells reside within the CD62L(+) Tcm cell compartment and highlight the promising therapeutic potential of this immune cell subset.
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“Haematopoietic19, somatic14 and cancer stem cells20 in mice and humans have been identified via serial transplantation of limiting cell numbers into immunodeficient mice.”
From An autoimmune stem-like CD8 T cell population drives type 1 diabetes (2022) · cites this paper as [19]
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“The gold-standard assay to evaluate stem cell functions remains serial transplantation in animal models.”
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Metadata
- Authors
- Graef, P., Buchholz, V. R., Stemberger, C., Flossdorf, M., Henkel, L., Schiemann, M., Drexler, I., Höfer, T., Riddell, S. R., & Busch, D. H.
- Affiliations
- Technical University of Munich (DE)
- German Cancer Research Center (DE)
- Helmholtz Munich (DE)
- Düsseldorf University Hospital (DE)
- University of Washington (US)
- Corresponding author
- Busch, Dirk H.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 41
- Issue
- 1
- Pages
- 116-126
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2138073407
- Cited by
- 311
- References
- 70
- Citations by year
- 2026: 16 · 2025: 18 · 2024: 15 · 2023: 26 · 2022: 28 · 2021: 27 · 2020: 37 · 2019: 24 · 2018: 25 · 2017: 23 · 2016: 35 · 2015: 27 · 2014: 10
- FWCI
- 14.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Site cant be reached (submittedVersion)
- 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
- CD8+ central memory T cells, T cell stemness, immunological memory, self-renewal, multipotency, naive T cells, Listeria monocytogenes, L-selectin
- MeSH terms
- Animals, Cell Differentiation, Immunocompetence, Immunologic Memory, Listeriosis, Listeria monocytogenes, Lymphocyte Activation, Mice, Inbred C57BL, T-Lymphocyte Subsets, Immunotherapy, Adoptive, Mice, Knockout, CD8-Positive T-Lymphocytes, L-Selectin, Cell Lineage, Multipotent Stem Cells, Mice, Adult Stem Cells
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