Cited by 312T-cell and B-cell ImmunologyImmunotherapy and Immune ResponsesHematopoietic Stem Cell Transplantation

Serial Transfer of Single-Cell-Derived Immunocompetence Reveals Stemness of CD8+ Central Memory T Cells

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Graef, Patricia, Buchholz, Veit R., Stemberger, Christian, Flossdorf, Michael, Henkel, Lynette, Schiemann, Matthias, Drexler, Ingo, Höfer, Thomas +2 more·2014·Immunity

Abstract

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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  • Haematopoietic, somatic and cancer stem cells in mice and humans have been identified via serial transplantation of limiting cell numbers into immunodeficient mice.

    “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]

    The Discussion describes this study’s serial single-cell transfers as modeled on hematopoietic stem-cell studies, and the Results compare its recovery rate with that of single hematopoietic stem cells. Those passages support the hematopoietic analogy, but do not establish the claimed use of immunodeficient mice to identify hematopoietic stem cells in both mice and humans. The separately cited somatic and cancer stem-cell claims are not assessed here. (LLM, conf=0.83)

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  • The gold-standard assay to evaluate stem cell functions remains serial transplantation in animal models.

    “The gold-standard assay to evaluate stem cell functions remains serial transplantation in animal models.”

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  1. [66]66. Weissman, I.L. Stem cells: units of development, units of regeneration, and units in evolution Cell. 2000; 100:157-168 Full Text Full Text (PDF) Scopus (1535) PubMed Google Scholar

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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.
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
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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