CD95-dependent bystander lysis caused by CD4+ T helper 1 effectors.
CD95-dependent lysis of target cells by CD4+ cells raises important questions of specificity and its potential role in inflammation. Much of what we know about CD95L-dependent killing is in fact bystander killing because the T cells have been previously activated by pharmacologic reagents. In an effort to better understand its significance in a more physiologic setting, we have examined bystander lysis by Th1 cells stimulated by Ag and APC in a murine model system. We find that bystander lysis is readily stimulated by M phi APC but not some epithelial lines, even though they themselves are killed in a CD95-dependent process while serving as APC. Bystander activity requires close proximity between the T cell, the APC, and the bystander target because bystanders are not lysed during coculture in Transwells.
Wang
R
R
Department of Molecular Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Rogers
A M
AM
Ratliff
T L
TL
Russell
J H
JH
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D018920:Coculture Techniques; D018856:Cystitis, Interstitial / Q000276:immunology / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism*; D007739:L Cells; D008213:Lymphocyte Activation; D008223:Lymphoma / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000276:immunology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity; D011994:Recombinant Proteins / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D019459:Urothelium / Q000166:cytology / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D019014:fas Receptor; D007371:Interferon-gamma