title: Impact of different mesenchymal stromal cell types on T-cell activation, proliferation and migration.
abstract: Mesenchymal stromal cells (MSCs) isolated from different tissue sources may present distinct immunomodulatory profiles. As lymphocyte responses are a combination of several distinct steps, we evaluated and compared the impact of MSCs from different sources on the activation, proliferation and migration of T-cells. We demonstrated that tissue-derived MSCs have important immunomodulatory effects. AT-MSCs induced potent anti-proliferative and anti-inflammatory (IFN-γ downregulation) effects and differentially modulated several T-cell activation markers (CD23, CD26, CD45, and CD69). Among all the MSC types tested, only AT-MSCs induced significant downregulation of CD26 and CD45 expression. Of importance, AT-MSCs maintained a sustained expression of CD69. AT-MSCs, particularly following exposure to an inflammatory environment, promoted the migration of lymphocytes into their surrounding environment. The AT-MSCs may increase recruitment of T lymphocytes by upregulation of IL-8 and CCL5 secretion. Following their migration, T-cells interact with MSCs, which can impair lymphocyte proliferation and activation depending on their origin. Inflammatory T-cells appeared to be progressively suppressed, which may lead to a population of lymphocytes with a regulatory phenotype. These findings are relevant, as they increase our understanding of the different immunomodulatory effect of MSCs as well as their behavior in an inflammatory environment.
authors.affiliation: Laboratory of Clinical Cell Therapy, Institut Jules Bordet, Université Libre de Bruxelles (ULB), 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: D002465:Cell Movement / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D056747:Immunomodulation; D008213:Lymphocyte Activation / Q000276:immunology*; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D009928:Organ Specificity; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines