Characterization of perforin-based and Fas-based CTL-mediated cytotoxicity by using low molecular probes

In vitro assay systems for perforin-based and Fas-based cytolytic mechanisms mediated by cytotoxic T lymphocytes (CTL) have been established, and applied to known inhibitors and antibiotics. Thus far the following conclusions have been drawn by the identification and characterization of active compounds: (1) A sufficient amount of perforin is stocked in lytic granules, and de novo synthesis, glycosylation and intracellular transport through Golgi apparatus are not necessary for immediate use; (2) Acidification is essential to maintain the structure and function of lytic granules and to prevent perforin from proteolysis; (3) Fas-based cytotoxicity depends on the de novo RNA and protein synthesis, glycosylation and the intracellular transport through Golgi apparatus of possibly Fas ligand upon T cell activation.