Inhibitory effect of the immunosuppressant FK506 on apoptotic cell death induced by HIV-1 gp120.
Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 may play a central role in inducing immunoregulatory disorders after HIV infection. The apoptotic death of normal human peripheral blood mononuclear cells was induced by priming with gp120 followed by stimulation with an anti-T cell receptor (TCR) antibody. Tumor necrosis factor-alpha produced by gp120-binding macrophages may be important to induce this cell death. Treatment of gp120-primed cells with an immunosuppressant (FK506) before TCR signaling inhibited apoptotic cell death, and this blocking effect of FK506 was concentration dependent. FK506 did not have any influence on cell growth and viability over the range of concentrations tested. These findings suggest that FK506 is a potentially useful drug in delaying the onset of AIDS after HIV infection.
Sekigawa
I
I
Department of Medicine, Juntendo University, School of Medicine, Tokyo, Japan.
Koshino
K
K
Hishikawa
T
T
Kaneko
H
H
Takasaki
Y
Y
Hashimoto
H
H
Hirose
S
S
Inagaki
Y
Y
Yamamoto
N
N
D000998:Antiviral Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D015699:HIV Envelope Protein gp120 / Q000633:toxicity*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D011485:Protein Binding / Q000187:drug effects; D016559:Tacrolimus / Q000494:pharmacology*
D000998:Antiviral Agents; D015699:HIV Envelope Protein gp120; D007166:Immunosuppressive Agents; D016559:Tacrolimus