Cell contact, prostaglandin E2 and transforming growth factor beta 1 play non-redundant roles in human mesenchymal stem cell induction of CD4+CD25Highforkhead box P3+ regulatory T cells
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- K English
- Institute of Immunology, National University of Ireland Maynooth, Maynooth, Co. Kildare
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- J M Ryan
- Institute of Immunology, National University of Ireland Maynooth, Maynooth, Co. Kildare
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- L Tobin
- Institute of Immunology, National University of Ireland Maynooth, Maynooth, Co. Kildare
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- M J Murphy
- Regenerative Medicine Institute (REMEDI), National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland
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- F P Barry
- Regenerative Medicine Institute (REMEDI), National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland
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- B P Mahon
- Institute of Immunology, National University of Ireland Maynooth, Maynooth, Co. Kildare
書誌事項
- 公開日
- 2009-02-03
- 権利情報
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- https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model
- DOI
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- 10.1111/j.1365-2249.2009.03874.x
- 公開者
- Oxford University Press (OUP)
この論文をさがす
説明
<jats:title>Summary</jats:title><jats:p>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)-β1 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-β1 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 E2 and TGF-β1 expression. Overall, this study provides a rational basis for ongoing clinical studies involving allogeneic MSC.</jats:p>
収録刊行物
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- Clinical and Experimental Immunology
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Clinical and Experimental Immunology 156 (1), 149-160, 2009-02-03
Oxford University Press (OUP)
