Activation of thymic regeneration in mice and humans following androgen blockade.
The thymus undergoes age-related atrophy, coincident with increased circulating sex steroids from puberty. The impact of thymic atrophy is most profound in clinical conditions that cause a severe loss in peripheral T cells with the ability to regenerate adequate numbers of naive CD4+ T cells indirectly correlating with patient age. The present study demonstrates that androgen ablation results in the complete regeneration of the aged male mouse thymus, restoration of peripheral T cell phenotype and function and enhanced thymus regeneration following bone marrow transplantation. Importantly, this technique is also applicable to humans, with analysis of elderly males undergoing sex steroid ablation therapy for prostatic carcinoma, demonstrating an increase in circulating T cell numbers, particularly naive (TREC+) T cells. Collectively these studies represent a fundamentally new approach to treating immunodeficiency states in humans.
Sutherland
Jayne S
JS
Department of Immunology, Monash University Medical School, Prahran, Victoria, Australia. j.sutherland@medsch.ucl.ac.uk
Goldberg
Gabrielle L
GL
Hammett
Maree V
MV
Uldrich
Adam P
AP
Berzins
Stuart P
SP
Heng
Tracy S
TS
Blazar
Bruce R
BR
Millar
Jeremy L
JL
Malin
Mark A
MA
Chidgey
Ann P
AP
Boyd
Richard L
RL
D000368:Aged; D000375:Aging / Q000502:physiology; D000726:Androgen Antagonists / Q000008:administration & dosage*; D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis; D017209:Apoptosis / Q000502:physiology; D001284:Atrophy; D016026:Bone Marrow Transplantation; D002369:Castration; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D038041:Lymphopoiesis / Q000187:drug effects / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D013950:Thymus Gland / Q000033:anatomy & histology / Q000187:drug effects / Q000473:pathology / Q000502:physiology*
D000726:Androgen Antagonists; D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D007987:Gonadotropin-Releasing Hormone; D019009:Proto-Oncogene Proteins c-kit