Figure 6

The inhibition of ADAM17 activity impairs both TNF-α release and HIV-1 replication in unstimulated CD4⁺T lymphocytes treated with exosomes from F12/Hut-78 cells. A. Effect of TAPI-2 on TNF-α release. 10⁵ unstimulated CD4⁺ T lymphocytes were challenged with 60 μU of exosomes from either Hut-78 or F12/Hut-78 cells, or, as control, treated with 2 μg/mL of PHA. After extensive washings, the cells were cultured for 6 hours in the presence or not (Nil) of the indicated concentrations of TAPI-2. Thereafter, supernatants were harvested and titrated for the presence of TNF-α. Shown are the mean + SD of TNF-α concentrations as calculated from three independent experiments with duplicates. *p < 0.05. B. Effect of TAPI-2 on HIV-1 replication. 10⁵ unstimulated CD4⁺ T lymphocytes were challenged with 60 μU of exosomes from either Hut-78 or F12/Hut-78 cells, and then infected by HIV-1. As control, unstimulated cells were challenged with HIV-1 alone, or in the presence of 2 μg/mL of PHA. The cells were then left in culture for 3 days in the presence or not (Nil) of the indicated concentrations of TAPI-2. Finally, the cells were analyzed for HIV-1 expression by FACS analysis. The fold increases of the percentages of HIV-1 CAp24-positive cells compared to cultures treated with HIV-1 alone are reported. Shown are the mean of fold increases + SD as calculated from three independent experiments with duplicates. *p < 0.05.