Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120.
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.
Westendorp
M O
MO
Tumorimmunology Program, German Cancer Research Centre, Heidelberg.
Frank
R
R
Ochsenbauer
C
C
Stricker
K
K
Dhein
J
J
Walczak
H
H
Debatin
K M
KM
Krammer
P H
PH
D000954:Antigens, Surface / Q000276:immunology*; D017209:Apoptosis; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003432:Cross-Linking Reagents; D053222:Fas Ligand Protein; D015696:Gene Products, tat / Q000097:blood / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000473:pathology; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured; D019014:fas Receptor; D054322:tat Gene Products, Human Immunodeficiency Virus
D000954:Antigens, Surface; D017252:CD3 Complex; D003432:Cross-Linking Reagents; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D015696:Gene Products, tat; D015699:HIV Envelope Protein gp120; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D019014:fas Receptor; D054322:tat Gene Products, Human Immunodeficiency Virus