TRAIL/Apo-2-ligand-induced apoptosis in human T cells

Eur J Immunol. 1998 Jan;28(1):143-52. doi: 10.1002/(SICI)1521-4141(199801)28:01<143::AID-IMMU143>3.0.CO;2-3.

Abstract

Members of the tumor necrosis factor (TNF) family such as CD95 (APO-1/Fas) ligand (L) trigger apoptosis in lymphoid cells. Recently, a new member of apoptosis-inducing ligands, TRAIL (TNF-related-apoptosis-inducing-ligand)/Apo-2 ligand, was identified that might act in a similar way. We compared TRAIL and CD95L-induced apoptosis in human lymphoid cells. Expression of TRAIL was found in CD4+ and CD8 T cells following activation, suggesting that TRAIL participates in T cell-mediated induction of apoptosis. Similar to CD95L, TRAIL-induced apoptosis in target cells is mediated by activation of caspases (ICE/Ced-3 proteases). However, different human lymphoid cell lines and peripheral T cells differ in sensitivity towards induction of apoptosis by TRAIL and CD95L. In addition, T cells are highly sensitive towards CD95L-induced apoptosis after prolonged activation in vitro, but remain completely resistant to TRAIL-induced apoptosis. In contrast, T cells from HIV-1-infected patients previously shown to exhibit increased CD95 sensitivity are even more susceptible towards TRAIL-induced cell death. These data suggest that TRAIL might participate in CD95-independent apoptosis of lymphoid cells and might be involved in deregulated apoptosis in diseases such as leukemias and HIV-1 infection.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins
  • Caspase 1
  • Caspase 3
  • Caspases*
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Cohort Studies
  • Cysteine Endopeptidases / metabolism
  • Enzyme Activation
  • Fas Ligand Protein
  • Gene Expression Regulation* / drug effects
  • HIV Infections / immunology
  • HIV Infections / pathology
  • HIV-1
  • Humans
  • Infant
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / genetics*
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / pharmacology
  • Membrane Glycoproteins / physiology*
  • RNA, Messenger / biosynthesis
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / pharmacology
  • Signal Transduction
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / drug effects
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tumor Necrosis Factor-alpha / physiology*

Substances

  • Apoptosis Regulatory Proteins
  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Cysteine Endopeptidases
  • Caspase 1