Effects of castration on thymocyte development in two different models of thymic involution. 2005

Tracy S P Heng, and Gabrielle L Goldberg, and Daniel H D Gray, and Jayne S Sutherland, and Ann P Chidgey, and Richard L Boyd
Department of Immunology, Monash University, Central and Eastern Clinical School, Alfred Hospital, Prahran, Australia.

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.

UI MeSH Term Description Entries
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009919 Orchiectomy The surgical removal of one or both testicles. Castration, Male,Orchidectomy,Castrations, Male,Male Castration,Male Castrations,Orchidectomies,Orchiectomies
D012038 Regeneration The physiological renewal, repair, or replacement of tissue. Endogenous Regeneration,Regeneration, Endogenous,Regenerations
D003520 Cyclophosphamide Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. (+,-)-2-(bis(2-Chloroethyl)amino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-Oxide Monohydrate,B-518,Cyclophosphamide Anhydrous,Cyclophosphamide Monohydrate,Cyclophosphamide, (R)-Isomer,Cyclophosphamide, (S)-Isomer,Cyclophosphane,Cytophosphan,Cytophosphane,Cytoxan,Endoxan,NSC-26271,Neosar,Procytox,Sendoxan,B 518,B518,NSC 26271,NSC26271
D006412 Hematopoietic Stem Cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Colony-Forming Units, Hematopoietic,Progenitor Cells, Hematopoietic,Stem Cells, Hematopoietic,Hematopoietic Progenitor Cells,Cell, Hematopoietic Progenitor,Cell, Hematopoietic Stem,Cells, Hematopoietic Progenitor,Cells, Hematopoietic Stem,Colony Forming Units, Hematopoietic,Colony-Forming Unit, Hematopoietic,Hematopoietic Colony-Forming Unit,Hematopoietic Colony-Forming Units,Hematopoietic Progenitor Cell,Hematopoietic Stem Cell,Progenitor Cell, Hematopoietic,Stem Cell, Hematopoietic,Unit, Hematopoietic Colony-Forming,Units, Hematopoietic Colony-Forming
D000375 Aging The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time. Senescence,Aging, Biological,Biological Aging
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001284 Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Atrophies

Related Publications

Tracy S P Heng, and Gabrielle L Goldberg, and Daniel H D Gray, and Jayne S Sutherland, and Ann P Chidgey, and Richard L Boyd
February 1997, Mechanisms of ageing and development,
Tracy S P Heng, and Gabrielle L Goldberg, and Daniel H D Gray, and Jayne S Sutherland, and Ann P Chidgey, and Richard L Boyd
January 2022, Frontiers in immunology,
Tracy S P Heng, and Gabrielle L Goldberg, and Daniel H D Gray, and Jayne S Sutherland, and Ann P Chidgey, and Richard L Boyd
October 2005, Seminars in immunology,
Tracy S P Heng, and Gabrielle L Goldberg, and Daniel H D Gray, and Jayne S Sutherland, and Ann P Chidgey, and Richard L Boyd
May 1981, Clinical and experimental immunology,
Tracy S P Heng, and Gabrielle L Goldberg, and Daniel H D Gray, and Jayne S Sutherland, and Ann P Chidgey, and Richard L Boyd
December 1989, Journal of immunology (Baltimore, Md. : 1950),
Tracy S P Heng, and Gabrielle L Goldberg, and Daniel H D Gray, and Jayne S Sutherland, and Ann P Chidgey, and Richard L Boyd
January 2018, Frontiers in immunology,
Tracy S P Heng, and Gabrielle L Goldberg, and Daniel H D Gray, and Jayne S Sutherland, and Ann P Chidgey, and Richard L Boyd
May 2007, Scandinavian journal of immunology,
Tracy S P Heng, and Gabrielle L Goldberg, and Daniel H D Gray, and Jayne S Sutherland, and Ann P Chidgey, and Richard L Boyd
January 1994, Thymus,
Tracy S P Heng, and Gabrielle L Goldberg, and Daniel H D Gray, and Jayne S Sutherland, and Ann P Chidgey, and Richard L Boyd
June 1957, British journal of pharmacology and chemotherapy,
Tracy S P Heng, and Gabrielle L Goldberg, and Daniel H D Gray, and Jayne S Sutherland, and Ann P Chidgey, and Richard L Boyd
December 2008, Ceska gynekologie,
Copied contents to your clipboard!