Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120

Nature. 1995 Jun 8;375(6531):497-500. doi: 10.1038/375497a0.


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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Surface / immunology*
  • Apoptosis*
  • CD3 Complex / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line
  • Cross-Linking Reagents
  • Fas Ligand Protein
  • Gene Products, tat / blood
  • Gene Products, tat / immunology*
  • HIV Envelope Protein gp120 / immunology*
  • HIV Infections / immunology
  • HIV Infections / pathology
  • Humans
  • Lymphocyte Activation
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocytes / immunology*
  • Tumor Cells, Cultured
  • fas Receptor
  • tat Gene Products, Human Immunodeficiency Virus


  • Antigens, Surface
  • CD3 Complex
  • Cross-Linking Reagents
  • FASLG protein, human
  • Fas Ligand Protein
  • Gene Products, tat
  • HIV Envelope Protein gp120
  • Membrane Glycoproteins
  • Receptors, Antigen, T-Cell
  • fas Receptor
  • tat Gene Products, Human Immunodeficiency Virus