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Tumor necrosis factor-related apoptosis-inducing ligand in T cell development: sensitivity of human thymocytes

A K Simon1, O Williams, J Mongkolsapaya

  • 1Medical Research Council Human Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom. katja.simon@ndm.ox.ac.uk

Proceedings of the National Academy of Sciences of the United States of America
|April 20, 2001
PubMed

Insights

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in tumor cells but not most primary cells. This study shows TRAIL resistance in peripheral T cells, unlike thymocytes, suggesting differential control in the immune system.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in tumor cells but not most primary cells, making it a potential cancer therapeutic.
  • The precise physiological role of TRAIL, particularly within the immune system, remains largely undefined.
  • TRAIL's involvement in target cell killing and lymphocyte death has been proposed but requires further investigation.

Purpose of the Study:

  • To investigate the role of TRAIL in lymphocyte development and function.
  • To determine the susceptibility of thymocytes and peripheral T cells to TRAIL-mediated apoptosis.
  • To elucidate the regulation of TRAIL receptor expression in different T cell populations.

Main Methods:

  • Development of a panel of monoclonal antibodies (mAbs) and soluble proteins targeting TRAIL.
  • Analysis of TRAIL receptor expression and apoptosis induction in thymocytes and peripheral T cells.
  • Utilizing various model systems to assess TRAIL's role in T cell activation and deletion.

Main Results:

  • Thymocytes exhibit activation-induced sensitization to TRAIL-mediated apoptosis, with corresponding upregulation of TRAIL receptors.
  • TRAIL does not appear to play a significant role in antigen-induced deletion of thymocytes.
  • Activated peripheral T cells do not upregulate TRAIL receptors and remain resistant to TRAIL-induced apoptosis.

Conclusions:

  • Susceptibility to TRAIL-induced apoptosis is differentially regulated in central (thymocytes) and peripheral T cells.
  • TRAIL's role in the immune system is complex and varies depending on the T cell subset and activation status.
  • These findings highlight distinct mechanisms controlling TRAIL sensitivity in different immune compartments.

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