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Blood, 1 August 2008, Vol. 112, No. 3, pp. 532-541. Prepublished online as a Blood First Edition Paper on April 29, 2008; DOI 10.1182/blood-2007-10-119370. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-10-119370v1 blood-2007-10-119370v2 112/3/532    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 CrossRef Google Scholar Articles by Karlsson, H. Articles by Amrolia, P. J. PubMed PubMed Citation Articles by Karlsson, H. Articles by Amrolia, P. J. Related Collections Transplantation Hematopoiesis and Stem Cells Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS Mesenchymal stem cells exert differential effects on alloantigen and virus-specific T-cell responses Helen Karlsson1,2, Sujith Samarasinghe1, Lynne M. Ball3, Berit Sundberg2, Arjan C. Lankester3, Francesco Dazzi4, Mehmet Uzunel2, Kanchan Rao5, Paul Veys5, Katarina Le Blanc2, Olle Ringdén2, and Persis J. Amrolia1,5 1 Molecular Immunology Unit, Institute of Child Health, London, United Kingdom; 2 Division of Clinical Immunology and Transfusion Medicine, Karolinska Institutet and Karolinska University Hospital Huddinge, Center for Stem Cell Transplantation, Stockholm, Sweden; 3 Department of Pediatrics, Leiden University Medical Centre, Leiden, The Netherlands; 4 Department of Haematology, Imperial College School of Medicine, London, United Kingdom; and 5 Department of Bone Marrow Transplantation, Great Ormond Street Hospital, London, United Kingdom Mesenchymal stem cells (MSCs) suppress alloantigen-induced T-cell functions in vitro and infusion of third-party MSCs seems to be a promising therapy for graft-versus-host disease (GVHD). Little is known about the specificity of immunosuppression by MSCs, in particular the effect on immunity to pathogens. We have studied how MSCs affect T-cell responses specific to Epstein-Barr virus (EBV) and cytomegalovirus (CMV). We found that EBV- and CMV-induced proliferation and interferon- (IFN-) production from peripheral blood mononuclear cells (PBMCs) was less affected by third-party MSCs than the response to alloantigen and that MSCs had no effect on expansion of EBV and CMV pentamer-specific T cells. Established EBV-specific cytotoxic T cells (CTL) or CMV-CTL cultured with MSCs retained the ability to proliferate and produce IFN- in response to their cognate antigen and to kill virally infected targets. Finally, PBMCs from 2 patients who received MSCs for acute GVHD showed persistence of CMV-specific T cells and retained IFN- response to CMV after MSC infusion. In summary, MSCs have little effect on T-cell responses to EBV and CMV, which contrasts to their strong immunosuppressive effects on alloreactive T cells. These data have major implications for immunotherapy of GVHD with MSCs and suggest that the effector functions of virus-specific T cells may be retained after MSC infusion. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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