Effects of Castration on Thymocyte Development in Two Different Models of Thymic Involution

Heng, Tracy S P; Goldberg, Gabrielle L; Gray, Daniel H D; Sutherland, Jayne S; Chidgey, Ann P; Boyd, Richard L

doi:10.4049/jimmunol.175.5.2982

Cited by 216T-cell and B-cell ImmunologyHematopoietic Stem Cell TransplantationMyasthenia Gravis and Thymoma

Effects of Castration on Thymocyte Development in Two Different Models of Thymic Involution

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Heng, Tracy S P, Goldberg, Gabrielle L, Gray, Daniel H D, Sutherland, Jayne S, Chidgey, Ann P, Boyd, Richard L·2005·The Journal of Immunology

DOI 10.4049/jimmunol.175.5.2982

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Abstract

Age-associated thymic involution is accompanied by decreased thymic output. This adversely affects general immune competence and T cell recovery following cytoreductive treatments such as chemotherapy. A causal link between increasing sex steroids and age-related thymic atrophy is well established. Although castration has been demonstrated to regenerate the atrophied thymus, little is known about how this is initiated or the kinetics of thymocyte regeneration. The present study shows that although castration impacts globally across thymocyte development in middle-aged mice, the regenerative effects are initiated in the immature triple-negative compartment and early T lineage progenitors (ETP). Specifically, there was a reduction in number of ETP with age, which was restored following castration. There was, however, no change in ETP reconstitution potential in ETP at this age or following castration. Furthermore, in a chemotherapy-induced model of thymic involution, we demonstrate castration enhances intrathymic proliferation and promotes differentiation through the triple-negative program. Clinically, reversible sex steroid ablation is achieved hormonally, and thus presents a means of ameliorating immune inadequacies, for example, following chemotherapy for bone marrow transplantation. By improving our understanding of the kinetics of thymic recovery, this study will allow more appropriate timing of therapy to achieve maximal reconstitution, especially in the elderly.

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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 [33]
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 [33]
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 [9]

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Williams, K. M., Chu, Y., & Gress, R. E. (2005) · Blood · doi:10.1182/blood.v106.11.1271.1271
Improving sex steroid ablation-induced thymic recovery for clinical application
Hince, M. N. (2017) · Figshare · doi:10.26180/4546339
The role of sex steroids and gonadectomy in the control of thymic involution
Hince, M. N., Sakkal, S., Vlahos, K., Dudakov, J. A., Boyd, R. L., & Chidgey, A. P. (2008) · Cellular Immunology · doi:10.1016/j.cellimm.2007.10.007 · Cited by 138 · see citing works
Self-citation

Authors: Heng, T. S. P., Goldberg, G. L., Gray, D. H. D., Sutherland, J. S., Chidgey, A. P., & Boyd, R. L.
Affiliations: Monash University (AU)
ORCID: Heng, Tracy S P
Gray, Daniel H D
Sutherland, Jayne S
Chidgey, Ann P
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 2005-09-01
Volume: 175
Issue: 5
Pages: 2982-2993
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.175.5.2982
OpenAlex: W2115334221
Cited by: 216
References: 65
Citations by year: 2026: 5 · 2025: 4 · 2024: 4 · 2023: 2 · 2022: 8 · 2021: 10 · 2020: 15 · 2019: 8 · 2018: 7 · 2017: 10 · 2016: 9 · 2015: 18 · 2014: 6 · 2013: 9 · 2012: 12
FWCI: 4.61
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
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: castration, thymic involution, T cell development, thymus regeneration, sex steroids, thymic atrophy, T cell reconstitution, bone marrow transplantation, aging, immunosenescence
MeSH terms: Aging, Animals, Atrophy, Cyclophosphamide, Hematopoietic Stem Cells, Lymphocyte Activation, Male, Mice, Inbred C57BL, Orchiectomy, Regeneration, T-Lymphocytes, Thymus Gland, Interleukin-7, Cell Lineage, Mice

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Effects of Castration on Thymocyte Development in Two Different Models of Thymic Involution

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