Soluble HLA-G inhibits cell cycle progression in human alloreactive T lymphocytes

HLA-G is involved in regulating T cell responses. Various mechanisnis 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 N18 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 p27k', but not p21(cip), in activated T cells. HLA-G does not induce apoptosis of alloreactive T cells, but induces p27(kip1) and inhibits cell cycle progression.