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Methods to Assess Beta Cell Death Mediated by Cytotoxic T Lymphocytes
12:12

Methods to Assess Beta Cell Death Mediated by Cytotoxic T Lymphocytes

Published on: June 16, 2011

TNF-related apoptosis-inducing ligand death pathway-mediated human beta-cell destruction

D Ou1, D L Metzger, X Wang

  • 1Department of Pediatrics, University of British Columbia, Canada. daweiou@interchange.ubc.ca

Diabetologia
|December 19, 2002
PubMed
Abstract

Insights

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway induces apoptosis in human beta cells. However, normal islet cells have inhibitors that block this TRAIL death pathway.

Area of Science:

  • Immunology
  • Cell Biology
  • Endocrinology

Background:

  • Human beta cells are crucial for insulin production.
  • Apoptosis, or programmed cell death, plays a role in beta cell dysfunction.
  • The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway is implicated in cell death.

Purpose of the Study:

  • To investigate the role of the TRAIL pathway in human beta cell apoptosis.
  • To determine if TRAIL can induce cell death in human beta cells.

Main Methods:

  • Examined TRAIL and TRAIL receptor expression in human beta cell lines and primary islet cells using RT-PCR and flow cytometry.
  • Assessed TRAIL-mediated beta cell destruction via cytotoxicity assays and apoptosis detection.

Main Results:

  • Human beta cells express TRAIL receptors and TRAIL.
  • TRAIL induced significant cytotoxicity and apoptosis in beta cell lines, more so than other death ligands.
  • Normal primary islet cells showed resistance to TRAIL-induced apoptosis, which could be overcome by inhibiting protein synthesis or removing TRAIL-R3.

Conclusions:

  • The TRAIL death pathway is functional in human islet beta cells.
  • Unidentified inhibitors in normal islet cells confer resistance to TRAIL-induced apoptosis.

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