SOLUBLE HLA-G INHIBITS CELL CYCLE PROGRESSION IN HUMAN ALLOREACTIVE T LYMPHOCYTES

Abstract

A276 Aim: HLA-G is involved in regulating T cell responses and is associated with lower rejection in human transplantation. 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. Methods: Using stably transfected M8 cells expressing either the membrane (HLA-G1) or the secreted isoform (HLA-G5) of HLA-G we investigated it’s the role of HLA-G in inducing apoptosis and in controlling the cell cycle of activated T cells. Results: 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 DiOC6 and IP labelling. 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 more than 80 %. In contrast, it induced an accumulation of p27kip but not p21cip in activated T cells. Conclusion: HLA-G does not induce apoptosis of alloreactive T cells but inhibits the progression through the cell cycle by regulating p27kip.