Multiple prethymic defects underlie age-related loss of T progenitor competence
Open accessAbstract
Aging in mice and humans is characterized by declining T-lymphocyte production in the thymus, yet it is unclear whether aging impacts the T-lineage potential of hematopoietic progenitors. Although alterations in the lymphoid progenitor content of aged mouse bone marrow (BM) have been described, irradiation-reconstitution experiments have failed to reveal defects in T-lineage potential of BM hematopoietic progenitors or purified hematopoietic stem cells (HSCs) from aged mice. Here, we assessed T-progenitor potential in unmanipulated recipient mice without conditioning irradiation. T-progenitor potential was reduced in aged BM compared with young BM, and this reduction was apparent at the earliest stages of intrathymic differentiation. Further, enriched populations of aged HSCs or multipotent progenitors (MPPs) gave rise to fewer T-lineage cells than their young counterparts. Whereas the T-precursor frequency within the MPP pool was unchanged, there was a 4-fold decline in T-precursor frequency within the HSC pool. In addition, among the T-competent HSC clones, there were fewer highly proliferative clones in the aged HSC pool than in the young HSC pool. These results identify T-compromised aged HSCs and define the nature and cellular sites of prethymic, age-related defects in T-lineage differentiation potential.
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The causes of age-related decline in lymphocyte development are multifactorial, involving changes in hematopoietic stem cells and progenitors as well as local tissue and systemic environments.
“The causes of this age-related reduction in lymphocyte development are multifactorial and include changes in HSCs and progenitor cells (11,12) as well as the local tissue and systemic environments (13,14).”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [12]
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- Authors
- Zediak, V. P., Maillard, I., & Bhandoola, A.
- Affiliations
- Department of Pathology and Laboratory Medicine,
- University of Pennsylvania (US)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2007-08-15
- Volume
- 110
- Issue
- 4
- Pages
- 1161-1167
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC1939899
- OpenAlex
- W2022070851
- Cited by
- 79
- References
- 53
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 1 · 2022: 3 · 2020: 3 · 2019: 4 · 2018: 1 · 2017: 5 · 2016: 2 · 2015: 8 · 2014: 3 · 2013: 7 · 2012: 9
- FWCI
- 5.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (T32CA009140, T32 CA 09140)
- National Institute of Allergy and Infectious Diseases (R56AI059621, R01AI059621)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- aging, hematopoietic stem cells, multipotent progenitors, T cell development, thymus, bone marrow
- MeSH terms
- Aging, Animals, Bone Marrow Cells, Cell Differentiation, Female, Hematopoietic Stem Cells, Mice, Inbred C57BL, T-Lymphocytes, Thymus Gland, Cell Lineage, Multipotent Stem Cells, Mice
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