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Cell contact, prostaglandin e2and transforming growth factor beta 1 play non-redundant roles in human mesenchymal stem cell induction of cd4+cd25highforkhead box p3+regulatory t cells

English, K.
; 
Ryan, J. M.
; 
Tobin, L.
; 
Murphy, M. J.
; 
Barry, F. P.
; 
Mahon, B. P.
Identifiers
http://hdl.handle.net/10379/11371
 https://doi.org/10.13025/27383
Publication Date
2009-04-01
Keywords
cell contact, mesnchymal stem cell, pge(2), regulatory t cell, tgf-beta 1, versus-host-disease, therapy position statement, stromal cells, dendritic cells, tgf-beta, lymphocyte-proliferation, controlling autoimmunity, international-society, peripheral-blood, interferon-gamma
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Article
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Citation
English, K. Ryan, J. M.; Tobin, L.; Murphy, M. J.; Barry, F. P.; Mahon, B. P. (2009). Cell contact, prostaglandin e2and transforming growth factor beta 1 play non-redundant roles in human mesenchymal stem cell induction of cd4+cd25highforkhead box p3+regulatory t cells. Clinical & Experimental Immunology 156 (1), 149-160
Abstract
Adult human mesenchymal stromal or stem cells (MSC) can differentiate into a variety of cell types and are candidate cellular therapeutics in regenerative medicine. Surprisingly, these cells also display multiple potent immunomodulatory capabilities, including allosuppression, making allogeneic cell therapy a possibility. The exact mechanisms involved in regulatory T cell induction by allogeneic human MSC was examined, using purified CD4(+) populations and well-characterized bone marrow-derived adult human MSC. Allogeneic MSC were shown to induce forkhead box P3 (FoxP3)(+) and CD25(+) mRNA and protein expression in CD4(+) T cells. This phenomenon required direct contact between MSC and purified T cells, although cell contact was not required for MSC induction of FoxP3 expression in an unseparated mononuclear cell population. In addition, through use of antagonists and neutralizing antibodies, MSC-derived prostaglandins and transforming growth factor (TGF)-beta 1 were shown to have a non-redundant role in the induction of CD4(+)CD25(+)FoxP3(+) T cells. Purified CD4(+)CD25(+) T cells induced by MSC co-culture expressed TGF-beta 1 and were able to suppress alloantigen-driven proliferative responses in mixed lymphocyte reaction. These data clarify the mechanisms of human MSC-mediated allosuppression, supporting a sequential process of regulatory T cell induction involving direct MSC contact with CD4(+) cells followed by both prostaglandin E-2 and TGF-beta 1 expression. Overall, this study provides a rational basis for ongoing clinical studies involving allogeneic MSC.
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Publisher
Wiley-Blackwell
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Attribution-NonCommercial-NoDerivs 3.0 Ireland
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Externally hosted open access publications with University of Galway authors (2)