BACKGROUND: The human leukocyte antigen-G (HLA-G) has been considered to be an important tolerogeneic molecule playing an essential role in maternal-fetal tolerance, which constitutes the perfect example of successful physiological immunotolerance of semi-allografts. In this context, we investigated the putative role of this molecule in the allogeneic hematopoietic cell transplantation setting. DESIGN AND METHODS: The percentage of HLA-G(+) cells in peripheral blood of healthy donors and allo-transplanted patients was evaluated by flow cytometry. Their immunoregulatory and tolerogeneic properties were investigated in in vitro immunostimulatory and immunosuppression assays. Immunohistochemical analysis for HLA-G expression was performed in skin biopsies from allo-transplanted patients and correlated with the occurrence of graft-versus-host disease. RESULTS: We identified a CD14(+)HLA-G(pos) population with an HLA-DR(low) phenotype and decreased in vitro immunostimulatory capacity circulating in peripheral blood of healthy individuals. Naturally occurring CD14(+)HLA-G(pos) cells suppressed T-cell responses and exerted an immunotolerogenic action on T cells by rendering them hyporesponsive and immunosuppressive in vitro. After allogeneic hematopoietic cell transplantation, HLA-G(pos) cells increase in blood. Interestingly, besides an increase in CD14(+)HLA-G(pos) cells, there was also a pronounced expansion of CD3(+)HLA-G(pos) cells. Of note, CD3(+)HLA-G(pos) and CD14(+)HLA-G(pos) cells from transplanted patients were suppressive in in vitro lymphoproliferation assays. Furthermore, we found an upregulation of HLA-G expression in skin specimens from transplanted patients that correlated with graft-versus-host disease. Inflammatory cells infiltrating the dermis of transplanted patients were also HLA-G(pos). CONCLUSIONS: We report the presence of naturally occurring HLA-G(pos) monocytic cells with in vitro suppressive properties. HLA-G expressing regulatory blood cells were found in increased numbers after allogeneic transplantation. Epithelial cells in skin affected by graft-versus-host disease revealed elevated HLA-G expression.
BACKGROUND: The human leukocyte antigen-G (HLA-G) has been considered to be an important tolerogeneic molecule playing an essential role in maternal-fetal tolerance, which constitutes the perfect example of successful physiological immunotolerance of semi-allografts. In this context, we investigated the putative role of this molecule in the allogeneic hematopoietic cell transplantation setting. DESIGN AND METHODS: The percentage of HLA-G(+) cells in peripheral blood of healthy donors and allo-transplanted patients was evaluated by flow cytometry. Their immunoregulatory and tolerogeneic properties were investigated in in vitro immunostimulatory and immunosuppression assays. Immunohistochemical analysis for HLA-G expression was performed in skin biopsies from allo-transplanted patients and correlated with the occurrence of graft-versus-host disease. RESULTS: We identified a CD14(+)HLA-G(pos) population with an HLA-DR(low) phenotype and decreased in vitro immunostimulatory capacity circulating in peripheral blood of healthy individuals. Naturally occurring CD14(+)HLA-G(pos) cells suppressed T-cell responses and exerted an immunotolerogenic action on T cells by rendering them hyporesponsive and immunosuppressive in vitro. After allogeneic hematopoietic cell transplantation, HLA-G(pos) cells increase in blood. Interestingly, besides an increase in CD14(+)HLA-G(pos) cells, there was also a pronounced expansion of CD3(+)HLA-G(pos) cells. Of note, CD3(+)HLA-G(pos) and CD14(+)HLA-G(pos) cells from transplanted patients were suppressive in in vitro lymphoproliferation assays. Furthermore, we found an upregulation of HLA-G expression in skin specimens from transplanted patients that correlated with graft-versus-host disease. Inflammatory cells infiltrating the dermis of transplanted patients were also HLA-G(pos). CONCLUSIONS: We report the presence of naturally occurring HLA-G(pos) monocytic cells with in vitro suppressive properties. HLA-G expressing regulatory blood cells were found in increased numbers after allogeneic transplantation. Epithelial cells in skin affected by graft-versus-host disease revealed elevated HLA-G expression.
Authors: P Moreau; F Adrian-Cabestre; C Menier; V Guiard; L Gourand; J Dausset; E D Carosella; P Paul Journal: Int Immunol Date: 1999-05 Impact factor: 4.823
Authors: Guillaume Monneret; Alain Lepape; Nicolas Voirin; Julien Bohé; Fabienne Venet; Anne-Lise Debard; Hélène Thizy; Jacques Bienvenu; François Gueyffier; Philippe Vanhems Journal: Intensive Care Med Date: 2006-06-02 Impact factor: 17.440