title: Long-lasting inhibitory effects of fetal liver mesenchymal stem cells on T-lymphocyte proliferation.
abstract: Human bone marrow mesenchymal stem cells (BM-MSC) are multipotent progenitor cells that have transient immunomodulatory properties on Natural Killer (NK) cells, Dendritic Cells (DC), and T cells. This study compared the use of MSC isolated from bone marrow and fetal liver (FL-MSC) to determine which displayed the most efficient immunosuppressive effects on T cell activation. Although both types of MSC exhibit similar phenotype profile, FL-MSC displays a much more extended in vitro life-span and immunomodulatory properties. When co-cultured with CD3/CD28-stimulated T cells, both BM-MSC and FL-MSC affected T cell proliferation by inhibiting their entry into the cell cycle, by inducing the down-regulation of phospho-retinoblastoma (pRb), cyclins A and D1, as well as up-regulating p27(kip1) expression. The T cell inhibition by MSC was not due to the soluble HLA-G5 isoform, but to the surface expression of HLA-G1, as shown by the need of cell-cell contact and by the use of neutralizing anti-HLA-G antibodies. To note, in a HLA-G-mediated fashion, MSC facilitated the expansion of a CD4(low)/CD8(low) T subset that had decreased secretion of IFN-γ, and an induced secretion of the immunomodulatory cytokine IL-10. Because of their longer lasting in vitro immunosuppressive properties, mainly mediated by HLA-G, and their more efficient induction of IL-10 production and T cell apoptosis, fetal liver MSC could be considered a new tool for MSC therapy to prevent allograft rejection.
authors.affiliation: U1014 INSERM, Hôpital Paul Brousse, Villejuif, France. giulianimas@hotmail.com
authors.forename: Massimo
authors.initials: M
authors.lastname: Giuliani
authors.forename: Maud
authors.initials: M
authors.lastname: Fleury
authors.forename: Amelia
authors.initials: A
authors.lastname: Vernochet
authors.forename: Farah
authors.initials: F
authors.lastname: Ketroussi
authors.forename: Denis
authors.initials: D
authors.lastname: Clay
authors.forename: Bruno
authors.initials: B
authors.lastname: Azzarone
authors.forename: Jean Jacques
authors.initials: JJ
authors.lastname: Lataillade
authors.forename: Antoine
authors.initials: A
authors.lastname: Durrbach
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D008099:Liver / Q000166:cytology / Q000196:embryology*; D008213:Lymphocyte Activation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology*
chemical_list: D015703:Antigens, CD; D006680:HLA Antigens