Host-reactive CD8+ memory stem cells in graft-versus-host disease
Abstract
Graft-versus-host disease (GVHD) is caused by alloreactive donor T cells that trigger host tissue injury. GVHD develops over weeks or months, but how this immune response is maintained over time is unknown. In mouse models of human GVHD, we identify a new subset of postmitotic CD44(lo)CD62L(hi)CD8(+) T cells that generate and sustain all allogeneic T-cell subsets in GVHD reactions, including central memory, effector memory and effector CD8(+) T cells, while self-renewing. These cells express Sca-1, CD122 and Bcl-2, and induce GVHD upon transfer into secondary recipients. The postmitotic CD44(lo)CD62L(hi)CD8(+) T cells persist throughout the course of GVHD, are generated in the initial phase in response to alloantigens and dendritic cells and require interleukin-15. Thus, their long life, ability to self-renew and multipotentiality define these cells as candidate memory stem cells. Memory stem cells will be important targets for understanding and influencing diverse chronic immune reactions, including GVHD.
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In a mouse model, CD44lowCD62Lhigh memory CD8+ T cells express high levels of Sca-1, Bcl-2, and CD122, and because they show robust self-renewal and multipotent capacity to generate central and effector memory T cells, they were designated T memory stem cells.
“In a mouse model, CD44lowCD62Lhigh memory CD8+ T cells express high levels of stem cell antigen-1 (Sca-1), Bcl-2 and common IL-2 and IL-15 receptor β chain (CD122). Because these cells showed robust self-renewal and the multipotent capacity to generate central memory and effector memory T cells, they were designated T memory stem cells [69].”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [69]
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References 50 · Cited by 369
- Authors
- Zhang, Y., Joe, G., Hexner, E., Zhu, J., & Emerson, S. G.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Emerson, Stephen G
- Venue
- Nature Medicine
- Published
- 2005-11-20
- Volume
- 11
- Issue
- 12
- Pages
- 1299-1305
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W1976460197
- Cited by
- 369
- References
- 50
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 16 · 2023: 23 · 2022: 16 · 2021: 16 · 2020: 21 · 2019: 21 · 2018: 20 · 2017: 15 · 2016: 17 · 2015: 23 · 2014: 19 · 2013: 22 · 2012: 26
- FWCI
- 4.61
- Type
- journal article
- Language
- en
- Update notices
- erratum (2005-12-01)
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Leukemia and Lymphoma Society
- National Cancer Institute (R01CA102464)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Transplantation › Organ and Tissue Transplantation Research
- Keywords
- graft-versus-host disease, self-renewal, IL-15, dendritic cells, alloantigen, Sca-1, CD122, Bcl-2, T cell memory subsets
- MeSH terms
- Animals, Antigens, Ly, Cell Differentiation, Cell Line, Flow Cytometry, Graft vs Host Disease, Immunologic Memory, Membrane Proteins, Stem Cells, Receptors, Interleukin-2, T-Lymphocyte Subsets, DNA Primers, Hematopoietic Stem Cell Transplantation, CD8-Positive T-Lymphocytes, Hyaluronan Receptors, L-Selectin, Proto-Oncogene Proteins c-bcl-2, Reverse Transcriptase Polymerase Chain Reaction, Mice
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