DUAL ROLE OF HIV TAT IN REGULATION OF APOPTOSIS IN T-CELLS

Apoptosis has been suggested to be one of the major mechanisms of depl etion of CD4(+) T cells in HIV-l-infected individuals. Remarkably, HIV -1-infected cells appear protected from apoptosis, whereas bystander c ells show increased apoptosis in lymph nodes of infected individuals. In this work, we present evidence that the trans-activating protein of HIV-1, Tat, has a dual role in regulation of apoptosis in T cells. Wh ile addition of exogenous Tat protein induced apoptosis in uninfected T cells, T cell clones stably expressing the Tat protein were protecte d from activation-induced apoptosis. The addition of exogenous Tat pot entiated anti-CD3 mAb, anti-fas IgM mAb, and TNF-alpha-induced apoptos is of T cells. Pretreatment of Tat with anti-Tat Ab abrogated Tat-indu ced apoptosis, but did not affect anti-fas IgM Ab-induced apoptosis. E ndogenously expressed Tat was analyzed in Jurkat T cell clones transfe cted with either full-length tat gene (101 amino acids), or in control cells containing an empty vector. The Tat101-transfected clones were resistant to anti-CD3-induced apoptosis, when compared with cells tran sfected with vector alone. Furthermore, cross-linking of CD4 molecules on T cells with gp160 and anti-gp160 Ab showed markedly decreased apo ptosis in Tat101 cells compared with that induced in cells transfected with vector alone. Taken together, our results indicate that HIV-1 Ta t can regulate apoptosis that may contribute to the immunopathogenesis of AIDS.