title: Dual role of HIV Tat in regulation of apoptosis in T cells.
abstract: Apoptosis has been suggested to be one of the major mechanisms of depletion of CD4+ T cells in HIV-1-infected individuals. Remarkably, HIV-1-infected cells appear protected from apoptosis, whereas bystander cells 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. While addition of exogenous Tat protein induced apoptosis in uninfected T cells, T cell clones stably expressing the Tat protein were protected from activation-induced apoptosis. The addition of exogenous Tat potentiated anti-CD3 mAb, anti-Fas IgM mAb, and TNF-alpha-induced apoptosis of T cells. Pretreatment of Tat with anti-Tat Ab abrogated Tat-induced apoptosis, but did not affect anti-Fas IgM Ab-induced apoptosis. Endogenously expressed Tat was analyzed in Jurkat T cell clones transfected 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 transfected with vector alone. Furthermore, cross-linking of CD4 molecules on T cells with gp160 and anti-gp160 Ab showed markedly decreased apoptosis in Tat101 cells compared with that induced in cells transfected with vector alone. Taken together, our results indicate that HIV-1 Tat can regulate apoptosis that may contribute to the immunopathogenesis of AIDS.
authors.affiliation: Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, NY 11030, USA.
authors.forename: T W
authors.initials: TW
authors.lastname: McCloskey
authors.forename: M
authors.initials: M
authors.lastname: Ott
authors.forename: E
authors.initials: E
authors.lastname: Tribble
authors.forename: S A
authors.initials: SA
authors.lastname: Khan
authors.forename: S
authors.initials: S
authors.lastname: Teichberg
authors.forename: M O
authors.initials: MO
authors.lastname: Paul
authors.forename: S
authors.initials: S
authors.lastname: Pahwa
authors.forename: E
authors.initials: E
authors.lastname: Verdin
authors.forename: N
authors.initials: N
authors.lastname: Chirmule
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects*; D015696:Gene Products, tat / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000187:drug effects*
chemical_list: D015696:Gene Products, tat