Activation of thymic regeneration in mice and humans following androgen blockade

Jayne S. Sutherland, Gabrielle L. Goldberg, Maree V. Hammett, Adam P. Uldrich, Stuart P. Berzins, Tracy S. Heng, Bruce R. Blazar, Jeremy L. Millar, Mark A. Malin, Ann P. Chidgey, Richard L. Boyd

Research output: Contribution to journalArticle

314 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2741-2753
Number of pages13
JournalJournal of Immunology
Volume175
Issue number4
DOIs
StatePublished - Aug 15 2005

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    Sutherland, J. S., Goldberg, G. L., Hammett, M. V., Uldrich, A. P., Berzins, S. P., Heng, T. S., Blazar, B. R., Millar, J. L., Malin, M. A., Chidgey, A. P., & Boyd, R. L. (2005). Activation of thymic regeneration in mice and humans following androgen blockade. Journal of Immunology, 175(4), 2741-2753. https://doi.org/10.4049/jimmunol.175.4.2741