Immunosuppressive effects of mesenchymal stem cells: involvement of HLA-G

Transplantation. 2007 Jul 27;84(2):231-7. doi: 10.1097/


Introduction: Mesenchymal stem cells (MSCs) possess unique immunomodulatory properties. They are able to suppress allogenic T-cell response and modify maturation of antigen-presenting cells. Their role in the treatment of severe graft versus host disease has been reported. The underlying molecular mechanisms of immunosuppression are currently being investigated. Histocompatibility locus antigen (HLA)-G is a nonclassical major histocompatibility complex class I antigen with strong immune-inhibitory properties.

Methods: We studied the role of HLA-G on MSC-induced immunosuppression. The expression of HLA-G on human MSCs cultured alone and in mixed lymphocytes reaction (MSC/MLR) was analyzed.

Results: We found that HLA-G can be detected on MSCs by real-time reverse-phase polymerase chain reaction, immunofluorescence, flow cytometry (52.4+/-3.6%), and enzyme-linked immunosorbent assay in the supernatant (38.7+/-5.2 ng/mL). HLA-G protein expression is constitutive and the level is not modified upon stimulation by allogenic lymphocytes in MSC/MLR. The functional role of HLA-G protein expressed by MSCs was analyzed using the 87G anti-HLA-G blocking antibody in a MSC/MLR. We found that blocking HLA-G molecule significantly raised lymphocyte proliferation in MSC/MLR (35.5%, P=0.01).

Conclusion: Our findings provide evidences supporting involvement of HLA-G in the immunosuppressive properties of MSCs. These results emphasize the potential application of MSCs as a relevant therapeutic candidate in transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow Cells / cytology
  • Cell Proliferation
  • Cells, Cultured
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene Expression*
  • Graft vs Host Disease / genetics
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / pathology
  • HLA Antigens / genetics*
  • HLA Antigens / immunology*
  • HLA Antigens / metabolism
  • HLA-G Antigens
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immunosuppression Therapy / methods*
  • Mesenchymal Stem Cell Transplantation / adverse effects
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / immunology*
  • Mesenchymal Stem Cells / metabolism
  • RNA, Messenger / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / immunology


  • HLA Antigens
  • HLA-G Antigens
  • Histocompatibility Antigens Class I
  • RNA, Messenger