The role of HLA-G in bone marrow transplantation

• Κύριος συγγραφέας: Λαζανά, Ιωάννα
• Άλλοι συγγραφείς: Σπυριδωνίδης, Αλέξανδρος
• Μορφή: Thesis
• Γλώσσα: English
• Έκδοση: 2014
• Θέματα: HLA-G; Monocytes; GvHD; Bone marrow transplantation; Immunoregulation; Immunosuppression; T regulatory cells; Skin; Μονοκύτταρα; Νόσος του μοσχεύματος έναντι του ξενιστή; Μεταμόσχευση μυελού των οστών; Ανοσορρύθμιση; Ανοσοκαταστολή; Τ ρυθμιστικά κύτταρα; Δέρμα; 617.441 059 2

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.