Expression of TRAIL receptors in human autoreactive and foreign antigen-specific T cells

Cell Death Differ. 2000 Jul;7(7):637-44. doi: 10.1038/sj.cdd.4400692.

Abstract

Deletion of T cells due to apoptosis induction is a regulatory mechanism in the human immune system that may be impaired in autoimmune diseases such as multiple sclerosis (MS). Involvement of the apoptosis-mediating CD95/CD95 ligand system in MS has been demonstrated. Here, we report that (auto)antigen-specific human T cells are not killed in vitro by soluble TNF-related apoptosis-inducing ligand (TRAIL) although expressing death-inducing receptors, TRAIL receptor 1 (TRAIL-R1) and TRAIL-R2. Apoptosis was assessed by caspase activation and DNA fragmentation, receptor expression was detected by RT - PCR and flow cytometry. The (auto)antigen-specific T cells were also resistant to specific TRAIL-R1/TRAIL-R2-directed induction of apoptosis, indicating that coexpression of the truncated TRAIL-R3 and TRAIL-R4 in these T cells is not responsible for the observed resistance. Upon stimulation, levels of death-inducing TRAIL receptors decreased whereas TRAIL was up-regulated on the cell surface. In contrast to CD95, the role of TRAIL receptors in MS might not involve regulation of T cell vulnerability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology
  • Apoptosis Regulatory Proteins
  • Autoantigens / immunology
  • CD4-Positive T-Lymphocytes
  • Caspases / metabolism
  • Cells, Cultured
  • DNA Fragmentation
  • GPI-Linked Proteins
  • Glioma
  • Humans
  • Jurkat Cells
  • Membrane Glycoproteins / metabolism*
  • Multiple Sclerosis / immunology
  • Myelin Basic Protein / immunology
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Receptors, Tumor Necrosis Factor, Member 10c
  • Recombinant Proteins
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • TNF-Related Apoptosis-Inducing Ligand
  • Tetanus Toxoid / immunology
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor Decoy Receptors
  • Tumor Necrosis Factor-alpha / metabolism*
  • fas Receptor / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Autoantigens
  • GPI-Linked Proteins
  • Membrane Glycoproteins
  • Myelin Basic Protein
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Member 10c
  • Recombinant Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFRSF10A protein, human
  • TNFRSF10B protein, human
  • TNFRSF10C protein, human
  • TNFSF10 protein, human
  • Tetanus Toxoid
  • Tumor Necrosis Factor Decoy Receptors
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • Caspases