The aged thymus shows normal recruitment of lymphohematopoietic progenitors but has defects in thymic epithelial cells
Abstract
Aging is associated with reduced numbers of all thymocyte sub-populations, including early T-cell progenitors. However, it is unclear if this is due to inadequate recruitment of lymphohematopoietic progenitor cells (LPCs) to the aged thymus or to abnormal development of T cells within the thymus. We found that LPCs from young mice were recruited equally well to the thymi of young or aged mice and that thymic stromal cells (TSCs) from young and old mice expressed similar levels of P-selectin and CCL25, which are believed to mediate recruitment of LPCs to the adult thymus. However, the number of recruited thymocytes in old thymus was markedly reduced after two weeks, indicating that T-cell development or proliferation is defective in the aged thymus. We also found that LPCs from aged and young mice have similar capacities to seed a fetal thymus that was transplanted under the kidney capsule. Thymic epithelial cells (TECs) in aged mice had lower proliferative capacity and higher rate of apoptosis, compared with findings in young animals. In addition, immunofluorescence staining with antibodies to cortical and medullary TECs revealed that aged thymi had a disorganized thymic stromal architecture, combined with reduced cellularity of the medulla, and apoptosis of thymocyte sub-populations in the medullary microenvironment was increased, compared with that in young mice. We conclude that aging does not impair recruitment of LPCs to the thymus, but is characterized by abnormalities in thymic epithelial architecture, especially medullary TEC function that may provide sub-optimal support for thymic development of LPCs.
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The integrity of cortical and medullary thymic architecture and the presence of functional thymic epithelial cells are required to support and maintain thymopoiesis.
“The integrity of cortical and medullary thymic architecture and the presence of functional thymic epithelial cells are required to support and maintain thymopoiesis (164).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [164]
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- Authors
- Gui, J., Zhu, X., Dohkan, J., Cheng, L., Barnes, P. F., & Su, D.-M.
- Affiliations
- The University of Texas Health Science Center at Tyler (US)
- Sheng Jing Hospital (CN)
- National Center for Geriatrics and Gerontology (JP)
- Venue
- International Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-09-05
- Volume
- 19
- Issue
- 10
- Pages
- 1201-1211
- ISSN
- 0953-8178 (ISSN-L)
- 1460-2377
- OpenAlex
- W2132561227
- Cited by
- 115
- References
- 37
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 6 · 2023: 4 · 2022: 8 · 2021: 7 · 2020: 9 · 2019: 6 · 2018: 4 · 2017: 2 · 2016: 7 · 2015: 6 · 2014: 3 · 2013: 7 · 2012: 6
- FWCI
- 2.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R21AG031880)
- National Institute of Allergy and Infectious Diseases (R21AI064939)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Neurology › Myasthenia Gravis and Thymoma
- Keywords
- thymus aging, thymic epithelial cells, T cell development, thymic stromal cells, P-selectin, CCL25, thymic medulla, apoptosis, thymocyte proliferation, thymus transplantation
- MeSH terms
- Aging, Animals, Epithelial Cells, Fetus, Hematopoietic Stem Cells, Mice, Inbred C57BL, Thymus Gland, Apoptosis, P-Selectin, Chemokines, CC, Cell Proliferation, Mice, Lymphoid Progenitor Cells
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