Fas ligand-mediated bystander lysis of syngeneic cells in response to an allogeneic stimulus.
Using a mouse allospecific lymph node (LN) CTL (H-2b) response to transplanted cells (H-2k), effector cells were shown to lyse C3H/HeJ or L929-Fas (H-2k) target cells in either a perforin-dependent or a Fas ligand (FasL)-dependent manner. C3H/HeJ.lpr targets or L929 targets lacking Fas were not sensitive to these effectors generated in perforin-deficient (Po) mice. By contrast, C3H/HeJ.lpr target cells and L929 were as responsive as C3H/HeJ and L929-Fas targets to the effectors generated in perforin wild-type (P+/+) mice. To measure potential bystander lysis in allogeneic responses, these same effector LN from either C57BL/6 P+/+ or P(o) mice were examined for lysis of C3H/HeJ (or C3H/HeJ.lpr) or L929-Fas (or L929) cocultured with 51Cr-labeled C57BL/6 (H-2b) target cells. Bystander lysis of C57BL/6 targets was observed only in those allogeneic responses where FasL was the defined mechanism of lysis. By contrast, perforin-mediated lysis was restricted by allo-recognition. Syngeneic (H-2b) targets that were not sensitive to Fas-mediated lysis were not lysed in a bystander fashion. Depletion of subsets of LN Po effectors (b anti-k) demonstrated that CD4+ T cells were primarily responsible for FasL-mediated direct and bystander lysis. FasL-mediated bystander lysis was also observed in H-2k anti-b reactions, except when the effectors were FasL mutant (gld). These data suggest that CTL responses to foreign Ag may evoke a certain amount of collateral damage to local host Fas-sensitive cells.
Smyth
M J
MJ
Cellular Cytotoxicity Laboratory, The Austin Research Institute, Heidelberg, Victoria, Australia. mj_smyth@muwayf.unimelb.edu.au
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D053222:Fas Ligand Protein; D008024:Ligands; D008198:Lymph Nodes / Q000276:immunology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D051381:Rats; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D014181:Transplantation Immunology / Q000502:physiology*; D014184:Transplantation, Homologous; D019014:fas Receptor / Q000502:physiology*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; C505662:Faslg protein, rat; D008024:Ligands; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D019014:fas Receptor; D054353:Perforin