Reduction in the Developmental Potential of Intrathymic T Cell Progenitors with Age
Open accessAbstract
Current models of thymic involution propose that intrinsic developmental defects in intrathymic T cell precursors do not contribute to age-related declines in thymopoiesis. This premise was reassessed in a murine model in light of the recent definition of the early T lineage progenitor (ETP), which appears to be the earliest intrathymic precursor defined to date. The results demonstrate that the frequency of ETP declines with age and their potential to reconstitute the thymus is diminished. These findings are consistent with the fact that ETP from aged mice proliferate less and have a higher rate of apoptosis than their counterparts from young animals. Taken together, these data suggest that age-associated changes in T cell precursors should be considered when attempts to rejuvenate the involuted thymus are made.
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Aging reduces the generation of B and T cells in the bone marrow and thymus and weakens the function of mature lymphocytes in secondary lymphoid tissues.
“The effects of aging on the immune system are manifest at multiple levels that include reduced production of B and T cells in bone marrow and thymus and diminished function of mature lymphocytes in secondary lymphoid tissues.”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [32]
The poor quality of lymphoid progenitors produced in aged animals worsens the decline in lymphopoiesis.
“In addition, the poor quality of the lymphoid progenitors that are generated in the aged further exacerbates the decline in lymphopoiesis (29,32,34).”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [32]
The number of B cell and T cell progenitors in the bone marrow and thymus is markedly reduced with age.
“In view of this, it is not surprising that the number of B cell (28)(29)(30)(31) and T cell (32,33) progenitors in bone marrow and thymus is markedly reduced with age.”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [32]
Common lymphoid progenitors, pre-pro-B cells, and pro-B cells from old mice proliferate less and undergo apoptosis more than young cells.
“For example, common lymphoid progenitors, pre-pro-B cells, and pro-B cells from old mice do not proliferate as extensively as do young cells, and they exhibit significantly higher rates of apoptosis.”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [32]
ETPs from old mice do not differentiate as efficiently as ETPs from young mice.
“In addition to proliferative defects, ETPs from old mice do not differentiate as efficiently as their young counterparts, 8”
From Fibroblast growth factor-7 partially reverses murine thymocyte progenitor aging by repression of Ink4a (2012) · cites this paper as [8]
ETPs from the involuted thymus retain impaired T-lymphopoietic potential when transferred into a young environment.
“because ETPs from the involuted thymus still exhibit impaired T-lymphopoietic potential when they are transferred to a young environment.8”
From Fibroblast growth factor-7 partially reverses murine thymocyte progenitor aging by repression of Ink4a (2012) · cites this paper as [8]
Early T-cell progenitors from the aged thymus have reduced proliferative capacity and increased apoptosis, which lowers their numbers.
“Early T-cell progenitors (ETPs), the most immature intrathymic Tcell precursors, harvested from the involuted thymus exhibit a diminished proliferative potential and increased rate of apoptosis and as a result their number is significantly reduced.”
From Fibroblast growth factor-7 partially reverses murine thymocyte progenitor aging by repression of Ink4a (2012) · cites this paper as [8]
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Cites
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- Authors
- Min, H., Montecino-Rodriguez, E., & Dorshkind, K.
- Affiliations
- University of California, Los Angeles (US)
- Department of Pathology and Laboratory Medicine and Hematopoietic Malignancies Program Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California , Los Angeles, CA 90095
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-07-01
- Volume
- 173
- Issue
- 1
- Pages
- 245-250
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2154124733
- Cited by
- 216
- References
- 1
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 10 · 2023: 5 · 2022: 7 · 2021: 5 · 2020: 10 · 2019: 7 · 2018: 11 · 2017: 6 · 2016: 10 · 2015: 11 · 2014: 6 · 2013: 9 · 2012: 13
- FWCI
- 4.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (CA16042)
- University of California, Los Angeles
- National Cancer Institute (CA-16 042, P30CA016042)
- Jonsson Comprehensive Cancer Center
- 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
- thymic involution, aging, thymopoiesis, thymus reconstitution, apoptosis, cell proliferation, T cell development
- MeSH terms
- Aging, Animals, Female, Hematopoietic Stem Cells, Lymphocyte Activation, Male, Mice, Inbred C57BL, T-Lymphocytes, Thymus Gland, Cell Lineage, Mice
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