FADDdel-GFP modified mouse insulinoma cells counteract the cytotoxicity of reactive T cells

Cell Mol Immunol. 2004 Oct;1(5):383-6.

Abstract

IDDM results from pancreatic beta cell destruction by islet-reactive T cells, a process that involves beta cell apoptosis. Fas-FasL pathway plays a major role in pancreatic beta cell death. Fas-associated death domain protein (FADD), the component of the tumor necrosis factor receptor type 1 (TNFR1) and Fas signaling complexes, is involved in TNFR1- and Fas-induced apoptosis. Inhibiting the function of FADD will lead to blocking downstream apoptosis signal, which protects pancreatic beta cells from destruction by Fas-FasL pathway. In this study we constructed eukaryotic expressing vector of fusional protein FADDdel-GFP named pFADDdel-GFP. After pFADDdel-GFP was transfected into NIT, the expression of FADDdel-GFP in NIT was detected by fluorescence microscopy and the resistance of NIT transfected with pFADDdel-GFP to cytotoxicity mediated by special T cells was detected by FACS and MTT. The results showed that NIT modified by pFADDdel-GFP obviously resisted cytotoxicity mediated by special T cells. Therefore, it may be useful in the prevention or treatment of IDDM by intervening Fas-FasL pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / immunology*
  • Animals
  • Apoptosis / immunology*
  • Cell Line, Tumor
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / therapy
  • Fas Ligand Protein
  • Fas-Associated Death Domain Protein
  • Insulin-Secreting Cells / immunology
  • Insulin-Secreting Cells / pathology
  • Insulinoma / immunology*
  • Membrane Glycoproteins / immunology
  • Mice
  • Receptors, Tumor Necrosis Factor / immunology
  • Receptors, Tumor Necrosis Factor, Type I
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Necrosis Factor Decoy Receptors
  • Tumor Necrosis Factors / immunology
  • fas Receptor / immunology

Substances

  • Adaptor Proteins, Signal Transducing
  • Fadd protein, mouse
  • Fas Ligand Protein
  • Fas-Associated Death Domain Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Tumor Necrosis Factor Decoy Receptors
  • Tumor Necrosis Factors
  • fas Receptor
  • recombinant human tumor necrosis factor-binding protein-1