title: Bone Marrow Mesenchymal Stromal Cells Induce Proliferative, Cytokinic and Molecular Changes During the T Cell Response: The Importance of the IL-10/CD210 Axis.
abstract: BACKGROUND
  Bone marrow mesenchymal stromal cells (BM-MSCs) display immunomodulatory features, representing a promising tool for cell-based therapies. However, the mechanisms used by MSCs to regulate T cell fate remain unclear.
  
  
  OBJECTIVE
  We investigated the potential of BM-MSCs to modulate T cell activation, proliferation, cytokine secretion and immunophenotype.
  
  
  METHODS
  T cells were co-cultured with BM-MSCs to assess their immunomodulatory impact. T cell characterization was performed using cell tracing, ELISA, intracellular and surface staining, flow cytometry analysis and qPCR.
  
  
  RESULTS
  The activation and proliferation of T cells were downregulated during coculture with BM-MSCs. We also observed that BM-MSCs upregulated IL-10 secretion as well as the expression of its receptor CD210 on T cells, thus creating a loop favoring the expansion of IL-10-producing T cells. IL-10 neutralization restored T cell proliferation, demonstrating that IL-10 is functionally relevant during immunomodulation. Moreover, BM-MSCs differently modulated CD4 and CD8 T-cell immunophenotype by inducing broad changes in their molecular pattern.
  
  
  CONCLUSIONS
  We provide a comprehensive functional and molecular characterization of T cells that are immunomodulated by BM-MSCs. Indeed, a better understanding of the immunological interplay between T cells and MSCs will facilitate the development of new efficient approaches to improve cell-based immune therapies.
authors.affiliation: Laboratory of Clinical Cell Therapy, Institute Jules Bordet, Université Libre de Bruxelles (ULB), Campus Erasme, Bâtiment de Transfusion (Level +1), Route de Lennik n° 808, 1070, Brussels, Belgium, mnajar@ulb.ac.be.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Najar
authors.forename: Gordana
authors.initials: G
authors.lastname: Raicevic
authors.forename: Hussein
authors.initials: H
authors.lastname: Fayyad-Kazan
authors.forename: Cécile
authors.initials: C
authors.lastname: De Bruyn
authors.forename: Dominique
authors.initials: D
authors.lastname: Bron
authors.forename: Michel
authors.initials: M
authors.lastname: Toungouz
authors.forename: Laurence
authors.initials: L
authors.lastname: Lagneaux
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D018920:Coculture Techniques; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000378:metabolism; D053709:Interleukin-10 Receptor alpha Subunit / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
chemical_list: C508609:IL10 protein, human; D053709:Interleukin-10 Receptor alpha Subunit; D016753:Interleukin-10