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

Original article


Nasef A, Mathieu N, Chapel A, Frick J, François S, Mazurier C, Boutarfa A, Bouchet S, Gorin NC, Thierry D, Fouillard L.

Inserm, U832, Université Pierre et Marie Curie-Paris6, Paris, France.

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


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.

Keywords: Immunosuppressive Effects of Mesenchymal Stem Cells: Involvement of HLA-G.