HIV-1-infected myelomonocytic cells are resistant to Fas-mediated apoptosis: effect of tumor necrosis factor-α on their Fas expression and apoptosis

To get insight into the involvement of tumor necrosis factor-α (TNF-α) and Fas (CD95) ligand in apoptosis (programmed cell death) of monocyte/macrophages in HIV-1-infected individuals, various T cell and myelomonocytic cell lines, including the HIV-1-infected clones OM-10.1 and U1 cells, were cultured in the presence of either TNF-α alone, anti-Fas agonist monoclonal antibody (Fas-mAb) alone, or their combinations. TNF-α moderately decreased the viability of myelomonocytic cell lines in a dose-dependent fashion (1–100 ng/ml). Unlike HIV-1-infected T cell lines, the viability of OM-10.1 and U1 cells was not affected by the treatment with Fas-mAb alone at concentrations up to 1,000 ng/ml. However, the viability of OM-10.1 cells further decreased with increasing concentrations of Fas-mAb when exposed simultaneously to TNF-α, suggesting that TNF-α sensitizes the cells to Fas-mAb-induced cell death. FACScan analysis and DNA gel electrophoresis revealed that the cell death was due to apoptosis. Such an effect of Fas-mAb was not identified in U1 cells. TNF-α but not Fas-mAb activated latent HIV-1 in OM-10.1 and U1 cells. Although all myelo-monocytic cell lines expressed Fas on their cell surface, TNF-α significantly up-regulated the expression of Fas in only OM-10.1 cells. These results indicate that, unlike T cells, HIV-1-infected myelomonocytic cells are generally resistant to the Fas-mediated apoptosis. However, they would become sensitive to the apoptosis if the expression of Fas could be up-regulated by TNF-α or other factors.