Leupeptin inhibition of the CD8+ cell-mediated suppression of HIV replication. The CNAR was measured against HIV-1SF33 acutely infected CD4+ T cells in the continued presence of the protease inhibitor leupeptin (A–E) or antipain (C) at the indicated CD8+ cell/CD4+ cell input ratios. The infected CD4+ target cells used were either heterologous (A–C) or autologous (D and E) with respect to the effector CD8+ cells, which were either PHA-stimulated (A and D) or nonstimulated (B, C, and E). The concentrations (in micrograms per milliliter) of the protease inhibitor used were 0 (■), 0.1 (), 1 (), and 10 (□) (see Tables 1 and 2 for molar equivalents). HIV replication was monitored every 3 d by measuring RT activity in culture fluid samples (28). The percent suppression of HIV replication was calculated by using RT values in the coculture fluids at the time of peak virus replication, typically on d 6 postinfection (see Materials and Methods). The level of RT activity in the fluids of untreated infected CD4+ cell control cultures always reached >200,000 cpm/ml at peak virus replication. The data are representative of three to eight separate experiments for each condition.