HIV-1 Tat Protein and Its Inhibitor Ro 24-7429 Inhibit Lymphocyte Proliferation and Induce Apoptosis in Peripheral Blood Mononuclear Cells from Healthy Donors

To explore further the effects of the HIV-1 transactivator protein Tat on human lymphoid cell function we examined the effects of Tat on lymphocyte proliferation and programmed cell death (apoptosis). We found that the HIV-1 Tat protein induced apoptosis and inhibited lymphocyte proliferative responses in lymphocytes obtained from healthy HIV-1-seronegative donors. Surprisingly, the Tat inhibitor Ro 24-7429 also induced apoptosis and inhibited antigen-induced lymphocyte proliferation. In checkerboard experiments, each agent could antagonize the effects of the other in both assays. These data suggest that Tat and its inhibitor may interact with a host element critically important in the processes of lymphocyte proliferation and programmed cell death. The HIV-1 Tat protein may affect both lymphocyte survival and function in HIV-1 infection, thereby contributing to the immune deficiency of HIV-1 disease.