HLA-G: foeto-maternal tolerance.

HLA-G: foeto-maternal tolerance. HLA-G is a non-classical major histocompat ibility complex class I molecule selectively expressed on cytotrophoblasts. We have demonstrated ex vivo (from voluntary pregnancy interruption sample s) the protector role of the HLA-G molecule present on the surface of cytot rophoblast cells versus the lysis carried out by the decidual uterine NK ce lls. This occurs under semi-allogenic conditions (maternal uterine NK cells and their trophoblast counterparts), as well as in allogenic conditions (m aternal uterine NK cells and trophoblast cells from different mothers), thu s defining the absence of maternal rejection at the moment of the implantat ion of the fertilized egg during pregnancy. Moreover, the expression of HLA -G on the cytotrophoblasts permits migration in maternal circulation and in filtration of maternal tissue (particularly in the skin), thereby probably creating a general state of tolerance. In the context of heart transplantat ion, in preliminary studies, we show that the presence of HLA-G in cardiac biopsy tissue prelevated from grafted patients significantly reduces acute rejects and shows an absence of chronic rejects. In the tumour context, the expression of HLA-G protein at the surface of primitive melanoma and metas tatic cells confers protection from NK and CTL lytic activity. This suggest s that HLA-G expression may impede the elimination of malignant cells by an ti-tumour immune effector cells, constituting a newly described mechanism b y which tumour cells may evade immunosurveillance. From there on E.D. Caros ella introduced the breakthrough concept of 'HLA a tolerance molecule' in t he heart of histocompatibility antigenes, which had been described up till then as antigenes of defence and rejection, and the dramatic role of HLA-G in immunotolerance. (C) 2000 Academie des sciences/Editions scientifiques e t medicales Elsevier SAS.