Induction of T Cell Development from Hematopoietic Progenitor Cells by Delta-like-1 In Vitro
Open accessAbstract
The molecular interactions provided by the thymic microenvironment that predicate T cell development remain obscure. Here, we show that a bone marrow stromal cell line ectopically expressing the Notch ligand Delta-like-1 loses its ability to support B cell lymphopoiesis, but acquires the capacity to induce the differentiation of hematopoietic progenitors into CD4 CD8 double- and single-positive T cells. Both gammadelta-TCR(+) and alphabeta-TCR(+) T cells are generated, and CD8(+) TCR(hi) cells produce gamma-interferon following CD3/TCR stimulation. These results establish that expression of Delta-like-1 on stromal cells provides key signals for the induction of T cell lineage commitment, stage-specific progenitor expansion, TCR gene rearrangement, and T cell differentiation in the absence of a thymus. Thus, it is likely that Delta-like-1/Notch interactions by the thymus underpin its unique ability to promote lineage commitment and differentiation of T cells.
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The extreme rarity of these very immature cells relative to later-stage thymocytes made them almost impossible to study in depth before the development of in vitro culture systems.
“Because of the extreme rarity of these very immature cells relative to the later-stage thymocytes at any given time, they were almost impossible to study in depth before the development of in vitro culture systems (88), which have continued to be informative to the present.”
From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [88]
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- Authors
- Schmitt, T. M., & Zúñiga-Pflücker, J. C.
- Affiliations
- Sunnybrook Health Science Centre (CA)
- ORCID
- Schmitt, Thomas M.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2002-12
- Volume
- 17
- Issue
- 6
- Pages
- 749-756
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2028735719
- Cited by
- 1,120
- References
- 1
- Citations by year
- 2026: 18 · 2025: 27 · 2024: 28 · 2023: 36 · 2022: 25 · 2021: 36 · 2020: 46 · 2019: 44 · 2018: 31 · 2017: 47 · 2016: 36 · 2015: 40 · 2014: 56 · 2013: 64 · 2012: 57
- FWCI
- 13.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3881 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- Delta-like 1, Notch signaling, T cell development, hematopoietic progenitor cells, mesenchymal stem cells, thymic microenvironment, T cell lineage commitment, CD4+CD8+ double-positive T cells, γδ T cells, alpha beta T cells, T-cell receptor gene rearrangement, interferon-gamma, ectopic thymus
- MeSH terms
- Animals, Bone Marrow Cells, Cell Differentiation, Cell Line, Hematopoietic Stem Cells, Membrane Proteins, Stromal Cells, Homeodomain Proteins, Gene Expression Regulation, Developmental, Cell Culture Techniques, Cell Lineage, Intracellular Signaling Peptides and Proteins, Mice
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