dc.contributor.author | English, K. | |
dc.contributor.author | Ryan, J. M. | |
dc.contributor.author | Tobin, L. | |
dc.contributor.author | Murphy, M. J. | |
dc.contributor.author | Barry, F. P. | |
dc.contributor.author | Mahon, B. P. | |
dc.date.accessioned | 2018-09-20T16:07:21Z | |
dc.date.available | 2018-09-20T16:07:21Z | |
dc.date.issued | 2009-04-01 | |
dc.identifier.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 | |
dc.identifier.issn | 0009-9104,1365-2249 | |
dc.identifier.uri | http://hdl.handle.net/10379/11371 | |
dc.description.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. | |
dc.publisher | Wiley-Blackwell | |
dc.relation.ispartof | Clinical & Experimental Immunology | |
dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Ireland | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/3.0/ie/ | |
dc.subject | cell contact | |
dc.subject | mesnchymal stem cell | |
dc.subject | pge(2) | |
dc.subject | regulatory t cell | |
dc.subject | tgf-beta 1 | |
dc.subject | versus-host-disease | |
dc.subject | therapy position statement | |
dc.subject | stromal cells | |
dc.subject | dendritic cells | |
dc.subject | tgf-beta | |
dc.subject | lymphocyte-proliferation | |
dc.subject | controlling autoimmunity | |
dc.subject | international-society | |
dc.subject | peripheral-blood | |
dc.subject | interferon-gamma | |
dc.title | 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 | |
dc.type | Article | |
dc.identifier.doi | 10.1111/j.1365-2249.2009.03874.x | |
dc.local.publishedsource | http://eprints.maynoothuniversity.ie/1291/1/BM2009_English_A.pdf | |
nui.item.downloads | 0 | |