[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 cytotoxicity, 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 proliferative 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.
Creput
C
C
SRHI, CEA, Hôpital Saint-Louis, Paris.
Durrbach
A
A
Charpentier
B
B
Carosella
E D
ED
Rouas-Freiss
N
N
D016207:Cytokines / Q000276:immunology; D006680:HLA Antigens / Q000097:blood / Q000378:metabolism*; D016027:Heart Transplantation / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D016030:Kidney Transplantation / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D016031:Liver Transplantation / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
D016207:Cytokines; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I