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 G Pahwa, Eric Verdin, Narendra Chirmule

Research output: Contribution to journalArticle

137 Citations (Scopus)

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

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HIV
Apoptosis
T-Lymphocytes
HIV-1
tat Gene Products
Clone Cells
tat Genes
CD4 Antigens
Jurkat Cells
Acquired Immunodeficiency Syndrome
Lymph Nodes
Amino Acids

ASJC Scopus subject areas

  • Immunology

Cite this

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

Dual Role of HIV Tat in Regulation of Apoptosis in T Cells. / McCloskey, Thomas W.; Ott, Melanie; Tribble, Eugene; Khan, Shabbir A.; Teichberg, Saul; Paul, Morris O.; Pahwa, Savita G; Verdin, Eric; Chirmule, Narendra.

In: Journal of Immunology, Vol. 158, No. 2, 15.01.1997, p. 1014-1019.

Research output: Contribution to journalArticle

McCloskey, TW, Ott, M, Tribble, E, Khan, SA, Teichberg, S, Paul, MO, Pahwa, SG, Verdin, E & Chirmule, N 1997, 'Dual Role of HIV Tat in Regulation of Apoptosis in T Cells', Journal of Immunology, vol. 158, no. 2, pp. 1014-1019.
McCloskey TW, Ott M, Tribble E, Khan SA, Teichberg S, Paul MO et al. Dual Role of HIV Tat in Regulation of Apoptosis in T Cells. Journal of Immunology. 1997 Jan 15;158(2):1014-1019.
McCloskey, Thomas W. ; Ott, Melanie ; Tribble, Eugene ; Khan, Shabbir A. ; Teichberg, Saul ; Paul, Morris O. ; Pahwa, Savita G ; Verdin, Eric ; Chirmule, Narendra. / Dual Role of HIV Tat in Regulation of Apoptosis in T Cells. In: Journal of Immunology. 1997 ; Vol. 158, No. 2. pp. 1014-1019.
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