Fas ligand mediates activation-induced cell death in human T lymphocytes.
A significant proportion of previously activated human T cells undergo apoptosis when triggered through the CD3/T cell receptor complex, a process termed activation-induced cell death (AICD). Ligation of Fas on activated T cells by either Fas antibodies or recombinant human Fas-ligand (Fas-L) also results in cytolysis. We demonstrate that these two pathways of apoptosis are causally related. Stimulation of previously activated T cells resulted in the expression of Fas-L mRNA and lysis of Fas-positive target cells. Fas-L antagonists inhibited AICD of T cell clones and staphylococcus enterotoxin B (SEB)-specific T cell lines. The data indicate AICD in previously stimulated T cells is mediated by Fas/Fas-L interactions.
Alderson
M R
MR
Immunex Research and Developmental Corporation, Seattle, Washington 98101.
Tough
T W
TW
Davis-Smith
T
T
Braddy
S
S
Falk
B
B
Schooley
K A
KA
Goodwin
R G
RG
Smith
C A
CA
Ramsdell
F
F
Lynch
D H
DH
D000954:Antigens, Surface / Q000502:physiology*; D017209:Apoptosis; D002478:Cells, Cultured; D053222:Fas Ligand Protein; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology*; D018613:Microscopy, Confocal; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019014:fas Receptor
D000954:Antigens, Surface; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate