Fas ligand-mediated depletion of CD4 and CD8 lymphocytes by monomeric HIV-1-gp120.
In order to determine in what condition and by what mechanism gp 120 can deplete not only CD4 but also CD8 T cells, an in vitro system was established in which peripheral blood lymphocytes from healthy donors were treated with recombinant gp 120. We found that gp 120 can deplete both CD4 and CD8 T cells when they have recently been activated and are exposed to IL-2-deficient conditions. Bioassay of the Fas ligand (FasL) demonstrated augmented expression and release of soluble FasL by CD4 T cells in the supernatant of this culture. The administration of anti-FasL mAb and anti-Fas mAb, both of which exhibit neutralizing activity, completely abolished the depletion of these two T cell populations in culture. Based on these findings, we concluded that FasL depletes Fas antigen expressing CD4 and CD8 T cells by programmed cell death.
Department of Infectious Diseases, Tokai Univesity School of Medicine, Kanagawa, Japan.
J
J
Uchiyama
S
S
Kishi
H
H
Yagita
S
S
Matsuzaki
Y
Y
Koga
D000911:Antibodies, Monoclonal; D017209:Apoptosis; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D053222:Fas Ligand Protein; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D015497:HIV-1; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D019014:fas Receptor / Q000032:analysis / Q000502:physiology
D000911:Antibodies, Monoclonal; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D015699:HIV Envelope Protein gp120; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D019014:fas Receptor