Delayed kinetics of tumor necrosis factor-mediated bystander lysis by peptide-specific CD8+ cytotoxic T lymphocytes

Eur J Immunol. 1998 Dec;28(12):4162-9. doi: 10.1002/(SICI)1521-4141(199812)28:12<4162::AID-IMMU4162>3.0.CO;2-E.


Mouse CD8+ CTL reactive with an H-2Db presented 9-mer peptide of the human papilloma virus 16 (HPV-16) protein E749-57 (RAHYNIVTF) were generated from the splenocytes of wild-type C57BL/6 (B6), B6.perforin-deficient, B6.gld or B6.TNF-deficient mice. In short-term (4 h) assays, CTL from B6, B6.TNF-deficient and B6.gld mice displayed peptide-specific perforin- and/or Fas ligand (FasL)-mediated lysis of E7-transfected mouse RMA lymphoma cells (RMA-E7) or E749-57 peptide-pulsed RMA-S cells, while CD8+ CTL from B6.perforin-deficient mice lysed via FasL exclusively. Rapid and efficient lysis of syngeneic bystander B6 spleen T cell blasts by B6, B6.TNF-deficient or B6.perforin-deficient antigen-activated CTL was mediated apparently exclusively by a FasL/Fas mechanism. By contrast CTL from B6.gld mice did not mediate rapid bystander lysis of B6 blasts. Rather B6.gld CTL delivered delayed bystander lysis after 36-48 h that was mediated by TNF. TNF-mediated bystander lysis of syngeneic blasts appeared to be independent of class I molecules and was mediated at least in part by soluble TNF. By contrast, there was no evidence that soluble FasL-mediated bystander lysis. For the first time, these data indicate that CD8+ CTL may use FasL or TNF in a kinetically and physically distinct fashion to mediate bystander killing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Death / immunology
  • Cytotoxicity, Immunologic*
  • Fas Ligand Protein
  • Gene Targeting
  • Humans
  • Membrane Glycoproteins / immunology
  • Mice
  • Oncogene Proteins, Viral / immunology*
  • Papillomavirus E7 Proteins
  • Time Factors
  • Tumor Necrosis Factor-alpha / immunology*
  • fas Receptor / immunology


  • FASLG protein, human
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • oncogene protein E7, Human papillomavirus type 16