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Blood, 1 March 2005, Vol. 105, No. 5, pp. 2214-2219. Prepublished online as a Blood First Edition Paper on October 28, 2004; DOI 10.1182/blood-2004-07-2921. This Article Full Text (PDF) All Versions of this Article: 2004-07-2921v1 105/5/2214    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 Beyth, S. Articles by Rachmilewitz, J. Search for Related Content PubMed PubMed Citation Articles by Beyth, S. Articles by Rachmilewitz, J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 2, 2004 Accepted October 21, 2004 Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T cell unresponsiveness Shaul Beyth, Zipora Borovsky, Dror Mevorach, Meir Liebergall, Zulma Gazit, Hadi Aslan, Eithan Galun, and Jacob Rachmilewitz* Goldyne Savad Institute of Gene Therapy, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Department of Orthopedic Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel Goldyne Savad Institute of Gene Therapy, Hadassah-Hebrew University Medical Center, Jerusalem, Israel The Laboratory for Cellular and Molecular Immunology, Rheumatology Unit, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel Department of Orthopedic Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel Skeletal Biotechnology Laboratory, Hebrew University-Hadassah Medical Center, Jerusalem, Israel * Corresponding author; email: rjacob{at}hadassah.org.il. Infusion of either embryonic or mesenchymal stem cells prolongs the survival of organ transplants derived from stem cell donors and prevents graft-versus-host-disease (GVHD). An in-depth mechanistic understanding of this tolerization phenomenon could lead to novel cell-based therapies for transplantation. Here we demonstrate that while human mesenchymal stem cells (hMSC) can promote superantigen-induced activation of purified T cells, addition of antigen-presenting cells (APC; either monocytes or dendritic cells) to the cultures inhibits the T cell responses. This contact- and dose-dependent inhibition is accompanied by secretion of large quantities of IL-10 and aberrant APC maturation, which can be partially overridden by the addition of factors that promote APC maturation (i.e., LPS or anti-CD40 mAb). Thus, our data support an immunoregulatory mechanism wherein hMSC inhibit T cells indirectly by contact-dependent induction of regulatory APC with T cell suppressive properties. 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