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Title: Activated T cells modulate immunosuppression by embryonic-and bone marrow-derived mesenchymal stromal cells through a feedback mechanism
Authors: Lin, W.
Oh, S.K.W.
George, A.J.T.
Keywords: Embryonic stem cells
Indoleamine-2,3- dioxygenase
Mesenchymal stromal cells
T cells
Issue Date: Mar-2012
Citation: Lin, W., Oh, S.K.W., CHOO BOON HWA,ANDRE, George, A.J.T. (2012-03). Activated T cells modulate immunosuppression by embryonic-and bone marrow-derived mesenchymal stromal cells through a feedback mechanism. Cytotherapy 14 (3) : 274-284. ScholarBank@NUS Repository.
Abstract: Background aims. 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. © 2012 Informa Healthcare.
Source Title: Cytotherapy
ISSN: 14653249
DOI: 10.3109/14653249.2011.635853
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