INHIBITION OF APOPTOSIS IN T-CELLS EXPRESSING HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I TAX

This study set out to determine whether T cell dysfunction associated with HTLV-I led to increased sensitivity of infected cells to apoptosi s or, owing to their potential to develop ATL, if infected cells would become resistant to this process. To test this hypothesis we utilized the monoclonal antibody anti-APO-1, which has been demonstrated to in duce apoptosis in human T cells. Human T cell lines expressing HTLV-I showed reduced susceptibility to anti-APO-1-induced apoptosis despite expression of high levels of cell surface APO-1. Cell-free supernatant of the Tax-expressing cell line C8166 and heat-inactivated supernatan t of the HTLV-I-producing cell line MT2 transferred increased resistan ce to anti-APO-1 to susceptible Jurkat T cells. Susceptible T cells tr ansfected with an HTLV-I Tax-expressing vector or treated with soluble Tax protein became less susceptible to anti-APO-1-induced cell death. Furthermore, primary human lymphocytes treated with soluble Tax were less susceptible to apoptosis induced by anti-APO-1. The protective ef fect of Tax in T cell lines and primary human lymphocytes was reversed by the addition of anti-Tax antibodies. Anti-APO-1-induced apoptosis was also found to be inhibited in Jurkat cells by the induction of pro tein kinase C (PKC) with 12-O-tetradecanoylphorbol-13-acetate (TPA). R esistance to apoptosis conferred by HTLV-I Tax and an active PKC pathw ay may be factors contributing to the survival of dysregulated HTLV-I- infected T cells prone to the development of adult T cell leukemia.