Fetal and Adult Hematopoietic Stem Cells Give Rise to Distinct T Cell Lineages in Humans
Open accessAbstract
Lymphocytes Layer It On: Cells of the immune system begin to develop from hematopoietic stem cells (HSCs) during fetal life. In the adult, HSCs continue to produce immune cells to replenish dying cells or in response to an infection. In mice and birds, immune cell development occurs in a “layered” manner, whereby distinct populations of HSCs that arise at different times during development generate distinct immune cell lineages. In contrast, development of human immune cells, and T lymphocytes in particular, is thought to be linear. Mold et al. (p. 1695 ; see the Perspective by Betz ) now show that T lymphocyte development in humans is also “layered,” and strategically so. T cells that arise from fetal HSCs are enriched in regulatory T cells, which promote immune tolerance, rather than classical T cells, which readily respond to foreign antigen. By favoring the development of regulatory T cell populations during fetal life, the immune system is perhaps better able to keep responses to maternal antigens in check. The development of large numbers of classical T cells is delayed until after birth when infectious agents represent a more imminent threat.
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Fetal naive CD4+ T cells tend to develop towards Foxp3+ CD25+ regulatory T cells through TGF-β, promoting self-tolerance.
“For example, though fetal naive CD4+ T cells respond strongly to alloantigens, they tend to develop towards Foxp3+ CD25+ regulatory T cells (Treg) through the influence of TGF-β [19], and thus actively promote self-tolerance.”
From Evolution of the immune system in humans from infancy to old age (2015) · cites this paper as [19]
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- Authors
- Mold, J. E., Venkatasubrahmanyam, S., Burt, T. D., Michaëlsson, J., Rivera, J. M., Galkina, S. A., Weinberg, K., Stoddart, C. A., & McCune, J. M.
- Affiliations
- University of California, San Francisco (US)
- Stanford Medicine (US)
- Karolinska Institutet (SE)
- Corresponding author
- Stoddart, Cheryl A.
- McCune, Joseph M.
- ORCID
- Venue
- Science
- Published
- 2010-12-17
- Volume
- 330
- Issue
- 6011
- Pages
- 1695-1699
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3276679
- OpenAlex
- W1983598990
- Cited by
- 444
- References
- 30
- Citations by year
- 2026: 13 · 2025: 22 · 2024: 24 · 2023: 25 · 2022: 30 · 2021: 44 · 2020: 34 · 2019: 21 · 2018: 22 · 2017: 30 · 2016: 36 · 2015: 23 · 2014: 35 · 2013: 30 · 2012: 32
- FWCI
- 11.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01ai70002-4-0-0, DP1OD000329)
- National Institute on Aging (R21AG033314, AG033314)
- National Cancer Institute (CA049605, P01CA049605)
- National Institute of Allergy and Infectious Diseases (AI-40312, R37AI040312, N01 AI070002, R01AI040312, P30AI027763)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- hematopoietic stem cells, fetal hematopoiesis, T cell development, regulatory T cells, immune tolerance, T cell lineage
- MeSH terms
- Adult, Aging, Animals, Bone Marrow, Bone Marrow Cells, Fetus, Hematopoietic Stem Cells, Humans, Immune Tolerance, Liver, Lymphocyte Activation, T-Lymphocytes, Thymus Gland, CD4-Positive T-Lymphocytes, Gene Expression, T-Lymphocyte Subsets, Mice, SCID, Cell Lineage, Cytoprotection, Oligonucleotide Array Sequence Analysis, Lymphopoiesis, T-Lymphocytes, Regulatory, Mice, Adult Stem Cells, Young Adult
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