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Cytotoxic CD8+ T cell molecule expression varies by location and memory status. Tissue residency reduces conventional cytotoxic molecules but environmental cues can modulate killing activity.

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Area of Science:

  • Immunology
  • Cellular Biology

Background:

  • CD8+ T cells are known for cytotoxic activity.
  • The compartmentalization of cytotoxic programs across tissues and memory subsets remains unclear.

Purpose of the Study:

  • To investigate the regulation of cytotoxic molecule expression in human CD8+ T cells.
  • To understand how tissue residency and environmental factors influence T cell cytotoxicity.

Main Methods:

  • Analysis of a human organ donor cohort.
  • In vitro studies using a tonsil system with transforming growth factor-β and interleukin-15.

Main Results:

  • Conventional cytotoxic molecules (granulysin, perforin, granzyme B) were highest in circulating memory CD8+ T cells and decreased with tissue residency.
  • Expression of other granzymes varied across tissues, with coordinated expression in virus-specific T cells.
  • Transforming growth factor-β and interleukin-15 modulated cytotoxic molecule expression, proliferation, and redirected killing activity.

Conclusions:

  • Human memory CD8+ T cell cytotoxicity is compartmentalized and influenced by tissue location.
  • Environmental cues, including cytokines, play a critical role in regulating T cell effector functions.