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Discrepancy between the in vitro and in vivo effects of murine mesenchymal stem cells on T cell proliferation and collagen-induced arthritis

2010; BioMed Central; Volume: 12; Issue: 1 Linguagem: Inglês

10.1186/ar2939

1478-6362

Evelien Schurgers, Hilde Kelchtermans, Tania Mitera, Lies Geboes, Patrick Matthys,

Periodontal Regeneration and Treatments

Abstract Introduction The goal of this study is to analyze the potential immunosuppressive properties of mesenchymal stem cells (MSC) on T cell proliferation and in collagen-induced arthritis (CIA). An additional aim is to investigate the role of interferon-γ (IFN-γ) in these processes. Methods MSC were isolated from bone marrow of DBA/1 wild type and IFN-γ receptor knock-out (IFN-γR KO) mice and expanded in vitro . Proliferation of anti-CD3-stimulated CD4 + T cells in the presence or absence of MSC was evaluated by thymidine incorporation. CIA was induced in DBA/1 mice and animals were treated with MSC by intravenous or intraperitoneal injections of wild type or IFN-γR KO MSC. Results Purity of enriched MSC cultures was evaluated by flow cytometry and their ability to differentiate into osteoblasts and adipocytes. In vitro , wild type MSC dose-dependently suppressed anti-CD3-induced T cell proliferation whereas IFN-γR KO MSC had a significantly lower inhibitory potential. A role for inducible nitric oxide (iNOS), programmed death ligand-1 (PD-L1) and prostaglandin E2 (PGE 2 ), but not indoleamine 2,3-dioxigenase (IDO), in the T cell inhibition was demonstrated. In vivo , neither wild type nor IFN-γR KO MSC were able to reduce the severity of CIA or the humoral or cellular immune response toward collagen type II. Conclusions Whereas MSC inhibit anti-CD3-induced proliferation of T cells in vitro , an effect partially mediated by IFN-γ, MSC do not influence in vivo T cell proliferation nor the disease course of CIA. Thus there is a clear discrepancy between the in vitro and in vivo effects of MSC on T cell proliferation and CIA.