Immunosuppressive Effects of Mesenchymal Stem Cells: Involvement of HLA-G
- 27 July 2007
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Transplantation
- Vol. 84 (2), 231-237
- https://doi.org/10.1097/01.tp.0000267918.07906.08
Abstract
International audienceINTRODUCTION: 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 transplantationKeywords
This publication has 29 references indexed in Scilit:
- Mesenchymal Stem Cells for Treatment of Therapy-Resistant Graft-versus-Host DiseaseTransplantation, 2006
- Cotransplantation of HLA-Identical Sibling Culture-Expanded Mesenchymal Stem Cells and Hematopoietic Stem Cells in Hematologic Malignancy PatientsTransplantation and Cellular Therapy, 2005
- Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cellsBlood, 2005
- Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsivenessBlood, 2005
- Human mesenchymal stem cells modulate allogeneic immune cell responsesBlood, 2005
- Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cellsThe Lancet, 2004
- Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuliBlood, 2002
- Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivoExperimental Hematology, 2002
- Rapid Hematopoietic Recovery After Coinfusion of Autologous-Blood Stem Cells and Culture-Expanded Marrow Mesenchymal Stem Cells in Advanced Breast Cancer Patients Receiving High-Dose ChemotherapyJournal of Clinical Oncology, 2000
- Cotransplantation of stroma results in enhancement of engraftment and early expression of donor hematopoietic stem cells in uteroExperimental Hematology, 1999