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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.
- Source :
- Clinical & Experimental Immunology; Apr2009, Vol. 156 Issue 1, p149-160, 12p, 5 Graphs
- Publication Year :
- 2009
-
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<superscript>+</superscript> populations and well-characterized bone marrow-derived adult human MSC. Allogeneic MSC were shown to induce forkhead box P3 (FoxP3)<superscript>+</superscript> and CD25<superscript>+</superscript> mRNA and protein expression in CD4<superscript>+</superscript> 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<superscript>+</superscript>CD25<superscript>+</superscript>FoxP3<superscript>+</superscript> T cells. Purified CD4<superscript>+</superscript>CD25<superscript>+</superscript> 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<superscript>+</superscript> cells followed by both prostaglandin E<subscript>2</subscript> and TGF-β1 expression. Overall, this study provides a rational basis for ongoing clinical studies involving allogeneic MSC. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00099104
- Volume :
- 156
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Clinical & Experimental Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 36867521
- Full Text :
- https://doi.org/10.1111/j.1365-2249.2009.03874.x