HLA-G: immunoregulatory molecule involved in allograft acceptance

The Human Leucocyte Antigen-G (HLA-G) is a non-classical MHC class I molecule of low polymorphism, restricted tissue distribution and tolerogeneic functions. It is clearly demonstrated that HLA-G contributes to fetal graft tolerance by the maternal immune system. The tolerogeneic properties of HLA-G act via specific inhibitory receptors present on immunocompetents cells. HLA-G inhibits natural killer cells (NK) and CD8+ T cell cytoxicity, suppresses CD4+ T cell proliferation in response to allogeneic stimulation and promotes T helper 2 (Th2) type responses. The soluble HLA-G protein is spontaneously secreted by allo-sensitized CD4+ T cells during mixed lymphocyte reactions (MLR), and inhibits their proliferation response. Finally, inhibition of dendritic cell maturation has been observed in HLA-G transgenic mice. In human organ transplantation, our group has reported in cardiac and liver-kidney transplanted patients, a positive correlation between the de novo ectopic expression of HLA-G in both patient's serum and graft biopsies, and a lower rate of acute rejection episodes of the grafts. Moreover no chronic graft rejection has been detected in those populations. These results support the involvement of HLA-G in regulatory mechanisms that may occur during human allotransplantation.