Delayed kinetics of tumor necrosis factor-mediated bystander lysis by peptide-specific CD8+ cytotoxic T lymphocytes.
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.
Smyth
M J
MJ
Cellular Cytotoxicity Laboratory, The Austin Research Institute, Heidelberg, Australia. m.smyth@ari.unimelb.edu.au
Sedgwick
J D
JD
D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016923:Cell Death / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D018390:Gene Targeting; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; C059731:oncogene protein E7, Human papillomavirus type 16