Περίληψη: | 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. The percentage of HLA-G+ cells in peripheral blood of healthy donors and allo-transplanted patients was evaluated by flow cytometry. Their immunoregulatory and immunotolerogeneic 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. We identified a CD14+
HLA-Gpos population with an HLA-DRlow
phenotype and decreased in vitro immunostimulatory capacity circulating in
peripheral blood of healthy individuals. Naturally occurring CD14+HLA-Gpos cells
suppressed T cell responses and acted immunotolerogenic on T cells by rendering
them hyporesponsive and immunosuppressive in vitro. After allogeneic hematopoietic cell transplantation, HLA-Gpos cells increase in blood. Interestingly, besides an increase of CD14+HLA-Gpos cells there was also a pronounced expansion of CD3+HLA-Gpos cells. Of note, CD3+HLA-Gpos and CD14+HLA-Gpos 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 which correlated with graft-versus-host disease. Inflammatory
cells infiltrating the dermis of transplanted patients were also HLA-Gpos. Here, we report the presence of naturally occurring HLA-Gpos monocytic cells with in vitro suppressive properties. HLA-G epressing 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.
|