Cutting edge: soluble HLA-G1 triggers CD95/CD95 ligand-mediated apoptosis in activated CD8+ cells by interacting with CD8.
The nonpolymorphic soluble HLA-G1 (sHLA-G1) isoform has been reported to be secreted by trophoblast cells at the materno-fetal interface, suggesting that it may act as immunomodulator during pregnancy. In this paper, we report that affinity-purified beta2-microglobulin-associated sHLA-G1 triggered apoptosis in activated, but not resting CD8+ peripheral blood cells. We demonstrate by Western blotting that sHLA-G1 enhanced CD95 ligand expression in activated CD8+ cells. Cytotoxicity was inhibited by preincubation of the cells with a CD95 antagonist mAb (ZB4) or a soluble recombinant CD95-Fc, indicating that apoptosis is mediated through the CD95/CD95 ligand pathway. Finally, we show that such sHLA-G1-induced apoptosis depends on the interaction with CD8 molecules, with cell death being blocked by various CD8 mAbs.
Fournel
S
S
Institut National de la Santé et de la Recherche Médicale (INSERM) U395, Hôpital de Purpan, Toulouse, France.
Aguerre-Girr
M
M
Huc
X
X
Lenfant
F
F
Alam
A
A
Toubert
A
A
Bensussan
A
A
Le Bouteiller
P
P
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000502:physiology; D017209:Apoptosis / Q000276:immunology*; D016827:CD8 Antigens / Q000378:metabolism* / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D053222:Fas Ligand Protein; D006680:HLA Antigens / Q000378:metabolism / Q000502:physiology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D012995:Solubility; D019014:fas Receptor / Q000378:metabolism / Q000502:physiology*
D000276:Adjuvants, Immunologic; D016827:CD8 Antigens; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor