Fas plays a role in Ca²⁺-independent T cell-mediated cytotoxicity. The study used thymocytes from lpr and gld mouse mutants and L1210 cells transfected with Fas to investigate Fas's involvement in T cell-mediated cytotoxicity. Both approaches showed that Fas is involved in the Ca²⁺-independent component of cytotoxicity mediated by non-antigen-specific in vitro-activated hybridoma cells and antigen-specific in vivo-raised peritoneal exudate lymphocytes. Fas transmits the death signal to target cells, leading to cell death. Programmed cell death, or apoptosis, is a key process in immune system development. Fas, a cell surface molecule, can transmit a death signal and is not or abnormally expressed in lpr mutant mice, which have a lymphoproliferative disorder. T cell-mediated cytotoxicity can cause cell death, and various molecular mechanisms are proposed, including direct membrane interactions and granule exocytosis. This study shows that Fas is involved in some instances of both nonspecific and antigen-specific Ca²⁺-independent T cell-mediated cytotoxicity. Fas is causally involved in cell death in both developmental and functional contexts within the immune system. The study used various cell lines and techniques to demonstrate Fas's role in cytotoxicity. Fas was cloned and transfected into L1210 cells, and the transfected cells were found to be sensitive to d10S cells. Northern blot analysis confirmed Fas expression in sensitive cells and not in insensitive cells. These results indicate that Fas is involved in the Ca²⁺-independent component of T cell-mediated cytotoxicity. The study also examined antigen-specific Ca²⁺-independent T cell-mediated cytotoxicity. Peritoneal exudate lymphocytes (PEL) were used as a model for antigen-specific cytotoxic T cells. PEL-mediated cytotoxicity showed two components: one requiring Ca²⁺ and one not. The Ca²⁺-independent component was antigen-specific and was not active in lpr thymocytes, which lack Fas. This suggests that the absence of Fas is directly responsible for the resistance of lpr thymocytes to Ca²⁺-independent PEL-mediated cytotoxicity. The study provides evidence that Fas is involved in both nonspecific and antigen-specific Ca²⁺-independent T cell-mediated cytotoxicity. Fas transmits a death signal to target cells, leading to cell death. The findings suggest that Fas is causally involved in cell death in both developmental and functional contexts within the immune system. The study also highlights the importance of Fas in immune system development and function.Fas plays a role in Ca²⁺-independent T cell-mediated cytotoxicity. The study used thymocytes from lpr and gld mouse mutants and L1210 cells transfected with Fas to investigate Fas's involvement in T cell-mediated cytotoxicity. Both approaches showed that Fas is involved in the Ca²⁺-independent component of cytotoxicity mediated by non-antigen-specific in vitro-activated hybridoma cells and antigen-specific in vivo-raised peritoneal exudate lymphocytes. Fas transmits the death signal to target cells, leading to cell death. Programmed cell death, or apoptosis, is a key process in immune system development. Fas, a cell surface molecule, can transmit a death signal and is not or abnormally expressed in lpr mutant mice, which have a lymphoproliferative disorder. T cell-mediated cytotoxicity can cause cell death, and various molecular mechanisms are proposed, including direct membrane interactions and granule exocytosis. This study shows that Fas is involved in some instances of both nonspecific and antigen-specific Ca²⁺-independent T cell-mediated cytotoxicity. Fas is causally involved in cell death in both developmental and functional contexts within the immune system. The study used various cell lines and techniques to demonstrate Fas's role in cytotoxicity. Fas was cloned and transfected into L1210 cells, and the transfected cells were found to be sensitive to d10S cells. Northern blot analysis confirmed Fas expression in sensitive cells and not in insensitive cells. These results indicate that Fas is involved in the Ca²⁺-independent component of T cell-mediated cytotoxicity. The study also examined antigen-specific Ca²⁺-independent T cell-mediated cytotoxicity. Peritoneal exudate lymphocytes (PEL) were used as a model for antigen-specific cytotoxic T cells. PEL-mediated cytotoxicity showed two components: one requiring Ca²⁺ and one not. The Ca²⁺-independent component was antigen-specific and was not active in lpr thymocytes, which lack Fas. This suggests that the absence of Fas is directly responsible for the resistance of lpr thymocytes to Ca²⁺-independent PEL-mediated cytotoxicity. The study provides evidence that Fas is involved in both nonspecific and antigen-specific Ca²⁺-independent T cell-mediated cytotoxicity. Fas transmits a death signal to target cells, leading to cell death. The findings suggest that Fas is causally involved in cell death in both developmental and functional contexts within the immune system. The study also highlights the importance of Fas in immune system development and function.