Immunosuppressive properties of human umbilical cord-derived mesenchymal stem cells: role of B7-H1 and IDO.
Umbilical cord is a rich source of mesenchymal stromal or stem cells (MSCs) that can be used for developing allogeneic cell therapy to treat intractable diseases. In this report, we present evidence that umbilical cord-derived MSCs (UCMSCs) possess important immunomodulatory properties that may enable them to survive in an allogeneic environment. UCMSCs do not express human leukocyte antigen (HLA)-DR and co-stimulatory molecules CD80 and CD86 that are required for T-cell activation. More importantly, UCMSCs constitutively express a negative regulator of T-cell activation, B7-H1, and its expression is increased after interferon-γ (IFN-γ) treatment. In addition, IFN-γ treatment induced indoleamine 2,3-dioxygenase (IDO) and HLA-DR expression in UCMSCs. Neither control nor IFN-γ-treated UCMSCs stimulated allogeneic T-cell proliferation, and both cell populations inhibited third-party dendritic cell (DC)-mediated allostimulatory activity. Addition of a B7-H1-specific blocking antibody or an IDO inhibitor, 1 methyl tryptophan (1-MT) abrogated the T-cell immunosuppressive activity of these cells. Furthermore, UCMSCs prevented the differentiation and maturation of peripheral blood monocyte-derived DCs, and augmented the generation of regulatory T cells (Tregs) in culture. The immunosuppressive effects of UCMSCs are largely mediated by cell-to-cell contact, although some inhibitory activity was observed with cell-free supernatant. Our study suggests that these immunomodulatory properties of UCMSCs could potentially improve the outcome of allogeneic stem cell therapy.
Tipnis
Shabari
S
Regenerative Medicine, Reliance Life Sciences Pvt Ltd, Dhirubhai Ambani Life Sciences Centre, Navi Mumbai, Maharashtra, India.
Viswanathan
Chandra
C
Majumdar
Anish S
AS
D019138:Antibodies, Blocking / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D060890:B7-H1 Antigen; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology; D005312:Fetal Blood / Q000166:cytology; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000473:pathology; D014364:Tryptophan / Q000031:analogs & derivatives / Q000494:pharmacology
D019138:Antibodies, Blocking; D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D006684:HLA-DR Antigens; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma; D014364:Tryptophan