Abstract
The depletion of CD4+ T cells in AIDS is correlated with high turnover of the human immunodeficiency virus HIV-1 and associated with apoptosis. The molecular mechanism of apoptosis in HIV infection, however, is largely unknown. T-cell apoptosis might be affected by viral proteins such as HIV-1 Tat and gp120 (refs 10, 11). T-cell-receptor (TCR)-induced apoptosis was recently shown to involve the CD95 (APO-1/Fas) receptor. We show here that HIV-1 Tat strongly sensitizes TCR- and CD4(gp120)-induced apoptosis by upregulation of CD95 ligand expression. Concentrations of Tat found to be effective in cultures of HIV-1-infected cells were also observed in sera from HIV-1-infected individuals. Taken together, our results indicate that HIV-1 Tat and gp120 accelerate CD95-mediated, activation-induced T-cell apoptosis, a mechanism that may contribute to CD4+ T-cell depletion in AIDS.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, Surface / immunology*
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Apoptosis*
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CD3 Complex / immunology
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / immunology
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Cell Line
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Cross-Linking Reagents
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Fas Ligand Protein
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Gene Products, tat / blood
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Gene Products, tat / immunology*
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HIV Envelope Protein gp120 / immunology*
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HIV Infections / immunology
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HIV Infections / pathology
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Humans
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Lymphocyte Activation
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism
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Receptors, Antigen, T-Cell / immunology
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T-Lymphocytes / immunology*
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Tumor Cells, Cultured
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fas Receptor
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tat Gene Products, Human Immunodeficiency Virus
Substances
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Antigens, Surface
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CD3 Complex
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Cross-Linking Reagents
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FASLG protein, human
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Fas Ligand Protein
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Gene Products, tat
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HIV Envelope Protein gp120
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Membrane Glycoproteins
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Receptors, Antigen, T-Cell
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fas Receptor
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tat Gene Products, Human Immunodeficiency Virus