Identification of IL-10 and TGF-beta transcripts involved in the inhibition of T-lymphocyte proliferation during cell contact with human mesenchymal stem cells
Titre de la revue : Gene expression
Volume : 13
N° : 4-5
Pagination : 217-226
Date de publication : 01/07/2007
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*Article de revue
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BOUCHET Sandrine, CHAPEL Alain, FOUILLARD Loïc, GORIN Norbert Claude, LOPEZ Manuel, MATHIEU Noëlle, MAZURIER Christelle, NASEF Aisha, SENSEBE Luc, THIERRY Dominique, ZHANG Yizhuo
Date de publication >
Mesenchymal stem cells (MSC) inhibit the response of allogeneic T lymphocytes in culture. Because the mechanisms of this effect may differ according to the existence of cell contact, we investigated the differences in gene expression of inhibitory molecules during MSC–T lymphocyte coculture when cell contact does and does not occur. Human MSC and T lymphocytes were cultured together in standard and transwell cultures. MSC gene expression was analyzed by semiquantitative real-time RT-PCR. MSC elicited a high dose-dependent inhibition of T lymphocytes in cultures with cell contact, but inhibition occurred even without cell contact. In both cases,we observed significant upregulation of IDO, LIF, and HLA-G, along with downregulation of HGF and SDF1.
In cultures with cell contact, IL-10 and TGF-β transcripts were expressed in a significantly higher level than in cultures without this contact. Furthermore, in the latter, the increased inhibition of T-cell proliferation was positively correlated with IDO gene expression and negatively correlated with SDF1 gene expression. MSC appear to induce T-cell tolerance by two distinct mechanisms. The first of these, which does not require cell contact, induces expression of the tolerogenic genes IDO, LIF, and HLA-G. The second mechanism, which is contact dependent, modulates IL-10 and TGF-β gene expression. These two mechanisms probably play separate roles in MSC-induced tolerance in allogeneic hematopoietic stem cell transplantation.