Involvement of two distinct killing mechanisms in bystander target cell lysis induced by a cytotoxic T lymphocyte clone.
Cytotoxic T lymphocyte (CTL) can lyse target cells by mainly two different mechanisms including granule exocytosis- and Fas-based cytotoxicity. In addition, CTL also lyse bystander target cells. In this study, we examined whether these two different killing mechanisms also cause bystander target cell lysis. EL-4 cells, representing bystander target cells, were incubated with CD8+ CTL clone B7B7 and antigen-treated P815 cells. EGTA-MgCl2 inhibited bystander lysis and reduced the release of BLT esterase. In addition, lysis of Fas-negative bystander cells (thymocytes from C57BL/6J-lpr/lpr not expressing Fas antigen) was also detected. CTL preactivated with antigen-treated P815 cells maintained a killing activity on bystander cells in the presence of cycloheximide (CHX). Furthermore, the presence of anti-Fas mAb inhibited the lysis of EL-4 cells by CTL stimulated with anti-TCR mAb. Thus, our results suggest that granule exocytosis- and Fas-mediated signal pathways cause the lysis of bystander target cells.
Kuwano
K
K
Department of Microbiology, Kurume University School of Medicine, Fukuoka, Japan.
Arai
S
S
D000818:Animals; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004533:Egtazic Acid / Q000494:pharmacology; D005089:Exocytosis / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D015636:Magnesium Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014176:Protein Biosynthesis; D015398:Signal Transduction / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019014:fas Receptor / Q000502:physiology
D019014:fas Receptor; D015636:Magnesium Chloride; D004533:Egtazic Acid