Activation-induced suicide of cytotoxic effectors in the presence of membrane-impermeant cathepsin B inhibitors. (A) Human CD8+ T cell blasts, resting blood CD8+ cells, CD4+ T cell blasts, and NK cells were incubated for 4 h with and without 50 μM cathepsin inhibitors ZLLY-DMK or ZFA-FMK. Cell death was assessed by propidium iodide from wells coated with control IgG (open inset bars) or the indicated degranulating stimuli (open bars). Striped bars, no inhibitor; solid bars, ZLLY-DMK; gray bars, ZFA-FMK.(B) Alloactivated mouse CD8+ T cell blasts were incubated for 4 h on anti-CD3–coated wells (solid bars) or control IgG (open inset bars) with or without 10 μM cystatin C or 50 μM ZLLY-DMK, and cell death was assessed by propidium iodide. (C) Alloactivated CD8+ BALB/c T cells were incubated on wells coated with anti-CD3 (solid bars) or control IgG (open inset bars) for 4 h in presence or absence of the indicated cathepsin inhibitors and stained with propidium iodide. (D) Same conditions as in C, comparing NS-196 and ZLLY-DMK.