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dc.contributor.authorEnglish, K.
dc.contributor.authorRyan, J. M.
dc.contributor.authorTobin, L.
dc.contributor.authorMurphy, M. J.
dc.contributor.authorBarry, F. P.
dc.contributor.authorMahon, B. P.
dc.date.accessioned2018-09-20T16:07:21Z
dc.date.available2018-09-20T16:07:21Z
dc.date.issued2009-04-01
dc.identifier.citationEnglish, 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.issn0009-9104,1365-2249
dc.identifier.urihttp://hdl.handle.net/10379/11371
dc.description.abstractAdult 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.publisherWiley-Blackwell
dc.relation.ispartofClinical & Experimental Immunology
dc.subjectcell contact
dc.subjectmesnchymal stem cell
dc.subjectpge(2)
dc.subjectregulatory t cell
dc.subjecttgf-beta 1
dc.subjectversus-host-disease
dc.subjecttherapy position statement
dc.subjectstromal cells
dc.subjectdendritic cells
dc.subjecttgf-beta
dc.subjectlymphocyte-proliferation
dc.subjectcontrolling autoimmunity
dc.subjectinternational-society
dc.subjectperipheral-blood
dc.subjectinterferon-gamma
dc.titleCell 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.typeArticle
dc.identifier.doi10.1111/j.1365-2249.2009.03874.x
dc.local.publishedsourcehttp://eprints.maynoothuniversity.ie/1291/1/BM2009_English_A.pdf
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