HIV-1 gp120-dependent induction of apoptosis in antigen-specific human T cell clones is characterized by 'tissue' transglutaminase expression and prevented by cyclosporin A.
We investigated the effect of cyclosporin (CsA) on HIV-gp120-dependent induction of cell death by apoptosis of human T cell clones specific for influenza virus haemagglutinin and restricted by HLA-DR1. Preincubation of the clones with gp120 induced a large inhibition of their proliferation which was paralleled by the induction of apoptosis. Exposure to the specific antigen alone was able to trigger apoptosis in a significant fraction of cells, this effect was potentiated by pretreatment with gp120. Apoptosis was characterized by the typical morphological changes and by the expression of 'tissue' Transglutaminase (tTG), one of the few characterized effector elements of programmed cell death. Interestingly, the tTG protein induction was detectable within the first 24 hours following the gp120 treatment and preceded the appearance of the typical apoptotic phenotype. Noteworthy, CsA treatment prevented the gp120-dependent induction of apoptosis by blocking the activation of the Ca(2+)-dependent effector elements such as tTG.
Amendola
A
A
Department of Biology, University of Rome Tor Vergata, Italy.
Lombardi
G
G
Oliverio
S
S
Colizzi
V
V
Piacentini
M
M
D017209:Apoptosis / Q000187:drug effects*; D002999:Clone Cells; D016572:Cyclosporine / Q000494:pharmacology*; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D015497:HIV-1; D015798:HLA-DR1 Antigen / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D011503:Transglutaminases / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000276:immunology
D015699:HIV Envelope Protein gp120; D015798:HLA-DR1 Antigen; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D014759:Viral Envelope Proteins; D016572:Cyclosporine; D011503:Transglutaminases