Identification of a novel HLA-G+ regulatory population in blood: expansion after allogeneic transplantation and de novo HLA-G expression at graft-versus-host disease sites
| Autor: | Dimitra Kokkinou, Anastasia Zoudiari, Maria Liga, Maria Themeli, Helen A. Papadaki, Alexandros Spyridonidis, Dionysios J. Papachristou, Ioanna Lazana |
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| Přispěvatelé: | VU University medical center |
| Rok vydání: | 2012 |
| Předmět: |
HLA-G Antigens
Allogeneic transplantation biology medicine.medical_treatment CD3 Graft vs Host Disease Immunosuppression Hematology Human leukocyte antigen medicine.disease Flow Cytometry Prognosis Immune tolerance Transplantation Graft-versus-host disease HLA-G Case-Control Studies Immunology medicine biology.protein Immune Tolerance Humans Transplantation Homologous Original Articles and Brief Reports Bone Marrow Transplantation |
| Zdroj: | Haematologica, 97(9), 1338-1347. Ferrata Storti Foundation Lazana, I, Zoudiari, A, Kokkinou, D, Themeli, M, Liga, M, Papadaki, H, Papachristou, D & Spyridonidis, A 2012, ' Identification of a novel HLA-G + regulatory population in blood : Expansion after allogeneic transplantation and de novo HLA-G expression at graft-versus-host disease sites ', Haematologica, vol. 97, no. 9, pp. 1338-1347 . https://doi.org/10.3324/haematol.2011.055871 |
| ISSN: | 1592-8721 0390-6078 |
| DOI: | 10.3324/haematol.2011.055871 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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