Dual Role of HIV Tat in Regulation of Apoptosis in T Cells

Thomas W. McCloskey, Melanie Ott, Eugene Tribble, Shabbir A. Khan, Saul Teichberg, Morris O. Paul, Savita Pahwa, Eric Verdin, Narendra Chirmule

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137 Scopus citations

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-I-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-α-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.

Original languageEnglish (US)
Pages (from-to)1014-1019
Number of pages6
JournalJournal of Immunology
Volume158
Issue number2
StatePublished - Jan 15 1997
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

McCloskey, T. W., Ott, M., Tribble, E., Khan, S. A., Teichberg, S., Paul, M. O., Pahwa, S., Verdin, E., & Chirmule, N. (1997). Dual Role of HIV Tat in Regulation of Apoptosis in T Cells. Journal of Immunology, 158(2), 1014-1019.