HIV-1 tat induced apoptosis of T-cells is not mediated by TGF-beta.

Recent reports have demonstrated that the HIV-1 transactivator protein, tat, induces apoptosis in T-lymphocyte cell lines, as well as in peripheral blood mononuclear cells, and stimulates a cascade of events resulting in up-regulation of the potent immunosuppressive cytokine, transforming growth factor-beta (TGF-beta). In this study we evaluated the ability of TGF-beta to mediate tat induced apoptosis in T-lymphocyte cell lines. T-cells treated exogenously with either TGF-beta1 or a combination of tat and pan-specific TGF-beta neutralizing antibodies showed little change in the amount of apoptosis. When treated with pan-specific TGF-beta neutralizing antibodies, Jurkat cells that stably express tat protein (Jurkat-tat ) showed only a modest decrease in apoptosis, while CEM-TART cells (CEM T-cells expressing both HIV-1 tat and rev ) demonstrated little change in the amount of apoptosis. In conclusion, we have demonstrated that TGF-beta does not play a significant role in mediating tat induced T-cell apoptosis.