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.
MeSH terms
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Aged
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Aging / physiology
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Androgen Antagonists / administration & dosage*
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Animals
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Antigens, Ly / biosynthesis
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Apoptosis / physiology
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Atrophy
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Bone Marrow Transplantation
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Castration
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Cell Differentiation / physiology
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Cell Proliferation
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Gonadotropin-Releasing Hormone / agonists*
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Humans
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Immunophenotyping
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / physiology*
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Lymphopoiesis / drug effects
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Lymphopoiesis / physiology
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Male
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Membrane Proteins / biosynthesis
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Middle Aged
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Proto-Oncogene Proteins c-kit / biosynthesis
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Regeneration / drug effects
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Regeneration / physiology*
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Stromal Cells / cytology
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Stromal Cells / physiology
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / physiology
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Thymus Gland / anatomy & histology
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Thymus Gland / drug effects
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Thymus Gland / pathology
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Thymus Gland / physiology*
Substances
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Androgen Antagonists
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Antigens, Ly
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Ly6a protein, mouse
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Membrane Proteins
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Gonadotropin-Releasing Hormone
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Proto-Oncogene Proteins c-kit