Immunosuppressive effects of mesenchymal stem cells: involvement of HLA-G.
BACKGROUND
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).


CONCLUSIONS
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.
Inserm, U832, Université Pierre et Marie Curie-Paris6, Paris, France.
Aisha
A
Nasef
Noelle
N
Mathieu
Alain
A
Chapel
Johanna
J
Frick
Sabine
S
François
Christelle
C
Mazurier
Asma
A
Boutarfa
Sandrine
S
Bouchet
N-Claude
NC
Gorin
Dominique
D
Thierry
Loïc
L
Fouillard
D001854:Bone Marrow Cells / Q000166:cytology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology / Q000473:pathology; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger