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Blood, 1 April 2005, Vol. 105, No. 7, pp. 2821-2827. Prepublished online as a Blood First Edition Paper on December 9, 2004; DOI 10.1182/blood-2004-09-3696. This Article Full Text (PDF) All Versions of this Article: 2004-09-3696v1 105/7/2821    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Glennie, S. Articles by Dazzi, F. Search for Related Content PubMed PubMed Citation Articles by Glennie, S. Articles by Dazzi, F. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 24, 2004 Accepted November 20, 2004 Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells Sarah Glennie, Ines Soeiro, Peter J Dyson, Eric W Lam, and Francesco Dazzi* Department of Immunology and Transplantation Biology, Faculty of Medicine, Imperial College London, London, United Kingdom Cancer Research-UK Labs and Department of Cancer Medicine, MRC Cyclotron Building, Imperial College London, Hammersmith Hospital, London, United Kingdom * Corresponding author; email: f.dazzi{at}imperial.ac.uk. It has been shown that mesenchymal stem cells (MSC) induce T cells to become unresponsive. We characterized the phenotype of these T cells by dissecting the effect of MSC on T cell activation, proliferation and effector function. For this purpose an in vitro murine model was used in which T cell responses are generated against the male HY minor histocompatibility antigen. In the presence of MSC, the expression of early activation markers CD25 and CD69 was unaffected but IFN- production was reduced. The inhibitory effect of MSC was directed mainly at the level of cell proliferation. Analysis of the cell cycle showed that T cells, stimulated in the presence of MSC, were arrested at the G1 phase. At the molecular level cyclinD2 expression was profoundly inhibited, whilst p27kip1 was upregulated. When MSC were removed from the cultures and restimulated with the cognate peptide, T cells produced IFN- but failed to proliferate. The addition of exogenous interleukin-2 did not restore proliferation. MSC did not preferentially target any T cell subset and the inhibition was also extended to B cells. MSC mediated inhibition induces an unresponsive T cell profile that is fully consistent with that observed in division arrest anergy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Aslam, R. Baveja, O. D. Liang, A. Fernandez-Gonzalez, C. Lee, S. A. Mitsialis, and S. Kourembanas Bone Marrow Stromal Cells Attenuate Lung Injury in a Murine Model of Neonatal Chronic Lung Disease Am. J. Respir. Crit. Care Med., December 1, 2009; 180(11): 1122 - 1130. [Abstract] [Full Text] [PDF] M. E.J. Reinders, W. E. Fibbe, and T. J. Rabelink Multipotent mesenchymal stromal cell therapy in renal disease and kidney transplantation Nephrol. Dial. Transplant., October 26, 2009; (2009) gfp552v1. 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