Human Mesenchymal Stem Cells Express HLA-G: Role in MSC Mediated Immunosuppressive Effect.

Mesenchymal stem cells (MSC) possess immunomodulatory properties, being able to suppress allogenic T cell response and modify maturation of antigen presenting cells. Recently its role for the treatment of graft versus host disease has been reported. The mechanisms of immunosuppression induced by MSC are being currently investigated.

HLA-G is a non-classical major histocompatibility complex (MHC) class I antigen HLA-G known by its strong immune-inhibtory property. We examined if HLA-G plays a role as a mediator of MSC induced immunosuppression. The expression of HLA-G on human MSC alone and in mixed lymphocytes reaction MSC/MLR was analyzed.

We found that HLA-G can be detected by RT-PCR, immunofluorescence, and by flow cytometry using intracellular staining (52.4 % ± 3.6). Using ELISA a level of 38.7 ± 5.2 ng/ml of soluble HLA-G was detected in the culture supernatant. HLA-G protein expression level is constitutive and is not modified upon stimulation by allogenic lymphocytes in MSC/MLR. We analysed the functional role of HLA-G protein expressed by MSC using anti HLA-G blocking antibody (87G). We found that blocking HLA-G protein can restore lymphocytes proliferation in MSC/MLR (25.4%, P= 0.04).

Our findings provide evidence supporting the immunosuppressive properties of MSC and the role of HLA-G. It emphasizes the potential application of MSC as a relevant therapeutic candidate in transplantation.