title: Identification of IL-10 and TGF-beta transcripts involved in the inhibition of T-lymphocyte proliferation during cell contact with human mesenchymal stem cells.
abstract: 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-beta 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-beta gene expression. These two mechanisms probably play separate roles in MSC-induced tolerance in allogeneic hematopoietic stem cell transplantation.
authors.affiliation: EA 1638 Laboratoire de Thérapie Cellulaire et Radioprotection Accidentelle, Faculté de médecine Saint Antoine, Université Paris VI, Paris, France.
authors.forename: Aisha
authors.initials: A
authors.lastname: Nasef
authors.forename: Alain
authors.initials: A
authors.lastname: Chapel
authors.forename: Christelle
authors.initials: C
authors.lastname: Mazurier
authors.forename: Sandrine
authors.initials: S
authors.lastname: Bouchet
authors.forename: Manuel
authors.initials: M
authors.lastname: Lopez
authors.forename: Noelle
authors.initials: N
authors.lastname: Mathieu
authors.forename: Luc
authors.initials: L
authors.lastname: Sensebé
authors.forename: Yizhuo
authors.initials: Y
authors.lastname: Zhang
authors.forename: Norbert-Claude
authors.initials: NC
authors.lastname: Gorin
authors.forename: Dominique
authors.initials: D
authors.lastname: Thierry
authors.forename: Loïc
authors.initials: L
authors.lastname: Fouillard
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology*; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D018920:Coculture Techniques; D005786:Gene Expression Regulation; D006801:Humans; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
chemical_list: C515255:CXCL12 protein, human; D015815:Cell Adhesion Molecules; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D016212:Transforming Growth Factor beta; D016753:Interleukin-10