Fas ligand (Fas-L) mediates activation-induced cell death (AICD) 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 AICD. Ligation of Fas on activated T cells by either Fas antibodies or recombinant human Fas-L results in cytolysis. The study demonstrates 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 that AICD in previously stimulated T cells is mediated by Fas/Fas-L interactions. Fas/APO-1 (CD95) is a protein expressed on the surface of various transformed cell lines and chronically stimulated T cells that can mediate apoptosis after ligation with a Fas-specific antibody. Under appropriate conditions, Fas also transduces a stimulatory signal to certain B cell lines and to freshly isolated human peripheral blood T cells and thymocytes. To investigate a possible relationship between CD3-stimulated AICD and Fas-mediated T cell apoptosis, the study used a mAb directed against human Fas (Fas M3). Immobilized Fas M3 mAb is able to lyse Fas-expressing tumor cell lines in a manner analogous to Fas-L or the prototypic Fas mAb, CH-11, whereas soluble Fas M3 blocks Fas-mediated killing. The study found that Fas-L induces apoptosis in human T cell clones. Immobilized Fas M3 mAb and recombinant human Fas-L (rFas-L) induce apoptosis in CD4+ TCC. Soluble Fas M3 mAb, which had no effect on PL-1 viability when added alone, efficiently blocked apoptosis induced by either rFas-L or immobilized Fas M3 mAb. Human T cell clones express Fas-L, and the study developed a sensitive bioassay to detect the presence of Fas-L using the Fas-sensitive human T cell line Jurkat as a target cell in a 51Cr-release cytotoxicity assay. PL-1 cells cultured in the presence of either PMA plus ionomycin or immobilized CD3 mAb induced lysis of Jurkat cells, whereas nonactivated TCC had little effect. The lysis of Jurkat target cells induced by either of these stimuli was almost completely inhibited by the addition of soluble Fas M3 mAb. The study also found that Fas antagonists block AICD in TCC. Fas antagonists inhibit AICD in TCC, and the interaction of thisFas ligand (Fas-L) mediates activation-induced cell death (AICD) 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 AICD. Ligation of Fas on activated T cells by either Fas antibodies or recombinant human Fas-L results in cytolysis. The study demonstrates 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 that AICD in previously stimulated T cells is mediated by Fas/Fas-L interactions. Fas/APO-1 (CD95) is a protein expressed on the surface of various transformed cell lines and chronically stimulated T cells that can mediate apoptosis after ligation with a Fas-specific antibody. Under appropriate conditions, Fas also transduces a stimulatory signal to certain B cell lines and to freshly isolated human peripheral blood T cells and thymocytes. To investigate a possible relationship between CD3-stimulated AICD and Fas-mediated T cell apoptosis, the study used a mAb directed against human Fas (Fas M3). Immobilized Fas M3 mAb is able to lyse Fas-expressing tumor cell lines in a manner analogous to Fas-L or the prototypic Fas mAb, CH-11, whereas soluble Fas M3 blocks Fas-mediated killing. The study found that Fas-L induces apoptosis in human T cell clones. Immobilized Fas M3 mAb and recombinant human Fas-L (rFas-L) induce apoptosis in CD4+ TCC. Soluble Fas M3 mAb, which had no effect on PL-1 viability when added alone, efficiently blocked apoptosis induced by either rFas-L or immobilized Fas M3 mAb. Human T cell clones express Fas-L, and the study developed a sensitive bioassay to detect the presence of Fas-L using the Fas-sensitive human T cell line Jurkat as a target cell in a 51Cr-release cytotoxicity assay. PL-1 cells cultured in the presence of either PMA plus ionomycin or immobilized CD3 mAb induced lysis of Jurkat cells, whereas nonactivated TCC had little effect. The lysis of Jurkat target cells induced by either of these stimuli was almost completely inhibited by the addition of soluble Fas M3 mAb. The study also found that Fas antagonists block AICD in TCC. Fas antagonists inhibit AICD in TCC, and the interaction of this