Soluble HLA-G inhibits cell cycle progression in human alloreactive T lymphocytes.
HLA-G is involved in regulating T cell responses. Various mechanisms have been proposed to explain the inhibition of T cell proliferation. In this context, the possible role of HLA-G in cell cycle regulation remains to be explored. Using stably transfected M8 cells expressing the secreted isoform (HLA-G5) of HLA-G, we investigated the role of HLA-G in inducing apoptosis and in controlling the cell cycle of activated T cells. Soluble HLA-G (HLA-G5) inhibited both CD4 and CD8 T cell proliferation. However, HLA-G5 did not induce T cell apoptosis, as determined by 3,3'-diethyloxacarbocyanine and propidium iodine labeling. It induced accumulation of the retinoblastoma protein, but not its phosphorylated and active form. Treatment of activated T cells with HLA-G5 also reduced the amounts of cyclin D2, E, A, and B by >80%. In contrast, it induced an accumulation of p27kip, but not p21cip, in activated T cells. HLA-G does not induce apoptosis of alloreactive T cells, but induces p27kip1 and inhibits cell cycle progression.
Bahri
Rajia
R
Institut National de la Santé et de la Recherche Médicale Unité 542, Villejuif, France.
Hirsch
Francois
F
Josse
Adeline
A
Rouas-Freiss
Nathalie
N
Bidere
Nicolas
N
Vasquez
Aime
A
Carosella
Edgardo D
ED
Charpentier
Bernard
B
Durrbach
Antoine
A
D017209:Apoptosis / Q000276:immunology; D002453:Cell Cycle / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D006131:Growth Inhibitors / Q000502:physiology*; D006680:HLA Antigens / Q000502:physiology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology*; D012995:Solubility; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D006131:Growth Inhibitors; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I