Homeostatic control of T-cell generation in neonates
Open accessAbstract
T cells are produced through 2 mechanisms, thymopoiesis and proliferative expansion of postthymic T cells. Thymic output generates diversity of the pool, and proliferation achieves optimal clonal size of each individual T cell. To determine the contribution of these 2 mechanisms to the formation of the initial T-cell repertoire, we examined neonates of 30 to 40 weeks' gestation. Peripheral T cells were in a state of high proliferative turnover. In premature infants, 10% of T cells were dividing; the proliferation rates then declined but were still elevated in mature newborns. Throughout the third trimester, concentrations of T-cell–receptor excision circles (TRECs) were 10 per 100 T cells. Stability of TREC frequencies throughout the period of repertoire generation suggested strict regulation of clonal size to approximately 10 to 20 cells. Neonatal naive CD4+ and CD8+ T cells were explicitly responsive to IL-7; growth-promoting properties of IL-15 were selective for newborn CD8+ T cells. Neonatal T cells expressed telomerase and, in spite of the high turnover, built up a telomeric reserve. Thus, proliferative expansion, facilitated by increased cytokine responsiveness, and thymopoiesis complement each other as mechanisms of T-cell production in neonates. Maintaining optimal clonal size instead of filling the space in a lymphopenic host appears to regulate homeostatic T-cell proliferation during fetal development.
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Substantial T cell proliferation is detected in cord blood of preterm infants when the T cell repertoire is established.
“substantial T cell proliferation is detected in cord blood of preterm infants when the T cell repertoire is established”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Schönland et al., 2003
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- Authors
- Schönland, S. O., Zimmer, J. K., Lopez-Benitez, C. M., Widmann, T., Ramin, K. D., Goronzy, J. J., & Weyand, C. M.
- Affiliations
- From the Departments of Medicine, Immunology, and Obstetrics and Gynecology, Mayo Clinic, Rochester, MN.
- Mayo Clinic (US)
- ORCID
- Weyand, Cornelia M.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2003-08-15
- Volume
- 102
- Issue
- 4
- Pages
- 1428-1434
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2076355973
- Cited by
- 178
- References
- 54
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 4 · 2023: 7 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 7 · 2018: 6 · 2017: 9 · 2016: 10 · 2015: 4 · 2014: 9 · 2013: 9 · 2012: 5
- FWCI
- 3.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Mayo Clinic
- National Institute on Aging (R01AG015043, R01AG15043)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR041974, R01 AR 41974, R01AR042527, R01AR42527)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Keywords
- thymopoiesis, TREC, T cell receptor repertoire, IL-7, IL-15, telomerase, CD4+ T cells, CD8+ T cells, preterm infants, fetal development, T cell homeostasis
- MeSH terms
- Adult, Cell Division, Cells, Cultured, Female, Fetal Blood, Hematopoiesis, Extramedullary, Homeostasis, Humans, Infant, Newborn, Insulin-Like Growth Factor I, Lymphocyte Activation, Male, T-Lymphocytes, CD4-Positive T-Lymphocytes, Interleukin-7, CD8-Positive T-Lymphocytes, Telomerase, Interleukin-15
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