Sex steroids induce apoptosis of CD8+CD4+ double-positive thymocytes via TNF-alpha

J A Guevara Patiño1, M W Marino, V N Ivanov

  • 1Immunology Program, Memorial Sloan-Kettering Cancer Center, New York 10021, USA.

Insights

Testosterone triggers thymus cell death by increasing TNF-alpha, a key mediator. This finding offers new ways to manage T cell production issues related to sex hormone imbalances.

Area of Science:

  • Immunology
  • Endocrinology

Background:

  • Thymic T cell production declines post-puberty, potentially due to sex steroids.
  • Sex steroids are known to influence thymic cellularity, with excess causing reduction and depletion causing increase.

Purpose of the Study:

  • To investigate the role of testosterone in thymocyte apoptosis.
  • To elucidate the mechanism by which testosterone affects thymic cellularity, specifically focusing on T cell development.

Main Methods:

  • Investigated the effect of testosterone on CD8+CD4+ double-positive (DP) thymocytes.
  • Utilized anti-TNF-alpha monoclonal antibodies and TNF-alpha knockout (TNF-alpha-/-) models in vivo.
  • Assessed testosterone's impact on TNF-alpha production and DP thymocyte sensitivity to TNF-alpha.

Main Results:

  • Testosterone specifically induces apoptosis in DP thymocytes through TNF-alpha.
  • Anti-TNF-alpha antibodies blocked testosterone-induced DP apoptosis.
  • DP thymocytes from TNF-alpha-/- mice showed resistance to testosterone-mediated apoptosis.

Conclusions:

  • TNF-alpha is the critical mediator of testosterone-induced thymocyte apoptosis.
  • Targeting TNF-alpha presents a potential therapeutic strategy for modulating T cell production in sex hormone-related disorders.

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