title: Activated T cells modulate immunosuppression by embryonic-and bone marrow-derived mesenchymal stromal cells through a feedback mechanism.
abstract: OBJECTIVE
  Human embryonic stem cell (hESC)-derived mesenchymal stromal cells (MSC) (hESC-MSC) are an alternative source of MSC to bone marrow (BM)-derived MSC (BM-MSC), which are being investigated in clinical trials for their immunomodulatory potential. hESC-MSC have the advantage of being consistent because each batch can be generated from hESC under defined conditions. In contrast, BM-MSC have a limited proliferative capacity.
  
  
  METHODS
  The ability to suppress the proliferation of anti-CD3/CD28-stimulated CD4 (+) T cells by hESC-MSC was compared with adult BM-MSC and neonatal foreskin fibroblast (Fb).
  
  
  RESULTS
  hESC-MSC suppress the proliferation of CD4 (+) T cells in both contact and transwell systems, although inhibition is less in the transwell system. hESC-MSC are approximately 2-fold less potent (67 cells/100 T cells) than BM-MSC and Fb (37 and 34 cells/100 T cells, respectively) at suppressing T-cell proliferation by 50% in a transwell [inhibitory concentration(IC)(50)]. The anti-proliferative effect is not contact-dependent but requires the presence of factors such as interferon (IFN)-γ produced by activated T cells. IFN-γ induces the expression of indoleamine-2,3-dioxygenase (IDO) in hESC-MSC, BM-MSC and Fb, contributing to their immunosuppressive property.
  
  
  CONCLUSIONS
  The feedback loop between MSC or Fb and activated T cells may limit the immunosuppressive effects of MSC and Fb to sites containing ongoing immunologic or inflammatory responses where activated T cells induce the up-regulation of IDO and immunomodulatory properties of MSC and Fb. These data demonstrate that hESC-MSC may be evaluated further as an allogeneic cell source for therapeutic applications requiring immunosuppression.
authors.affiliation: Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), Singapore.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Lin
authors.forename: Steve K W
authors.initials: SK
authors.lastname: Oh
authors.forename: Andre B H
authors.initials: AB
authors.lastname: Choo
authors.forename: Andrew J T
authors.initials: AJ
authors.lastname: George
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D025461:Feedback, Physiological; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D018106:CD28 Antigens; D017252:CD3 Complex; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma