Dual role of TNF-alpha in NK/LAK cell-mediated lysis of chronically HIV-infected U1 cells. Concomitant enhancement of HIV expression and sensitization of cell-mediated lysis

The U937-derived chronically HIV-infected U1 cell line and uninfected U937 cell clones were efficiently lysed by both unstimulated (NK) and IL-2-stimu lated (lymphokine-activated killer; LAK) peripheral blood mononuclear cells (PBMC) of healthy HIV-seronegative donors. Pretreatment of target cells wi th IFN-gamma down-modulated killing of both U1 cells and two U937 cell clon es, and up-regulated MHC class I expression. In contrast, TNF-alpha enhance d the sensitivity of infected U1 cells, but not of U937 cell clones to NK/L AK cell lysis. Co-cultivation of IL-2-stimulated PBMC with U1 cells trigger ed expression and replication of HIV by cell-cell contact, and this effect was inhibited by anti-TNF-alpha antibodies (Ab); virus production was parti ally inhibited by zidovudine. Of interest, anti-TNF-alpha Ab protected U1 c ells from LAK cell activity. Thus, TNF-alpha can induce HIV expression from chronically infected U1 cells, but also plays an important role in sensiti zing these cells to lysis.