Email updates

Keep up to date with the latest news and content from Arthritis Research & Therapy and BioMed Central.

Open Access Highly Accessed Research article

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

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

Author Affiliations

Laboratory of Immunobiology, Rega Institute, Faculty of Medicine, Katholieke Universiteit Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium

For all author emails, please log on.

Arthritis Research & Therapy 2010, 12:R31  doi:10.1186/ar2939


See related editorial by Scherer et al., http://arthritis-research.com/content/12/3/126

Published: 22 February 2010

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 (PGE2), 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.