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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.
 Previous Article | Table of Contents | Next Article 
TRANSPLANTATION
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
From the Goldyne Savad Institute of Gene Therapy; Department of Orthopedic Surgery; The Laboratory for Cellular and Molecular Immunology, Rheumatology Unit, Department of Medicine; and the Skeletal Biotechnology Laboratory, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
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 (hMSCs) can promote superantigen-induced activation of purified T cells, addition of antigen-presenting cells (APCs; 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 interleukin (IL)–10 and aberrant APC maturation, which can be partially overridden by the addition of factors that promote APC maturation (ie, lipopolysaccharide [LPS] or anti-CD40 monoclonal antibody [mAb]). Thus, our data support an immunoregulatory mechanism wherein hMSCs inhibit T cells indirectly by contact-dependent induction of regulatory APCs with T-cell–suppressive properties. Our data may reveal a physiologic phenomenon whereby the development of a distinct APC population is regulated by the tissue's cellular microenvironment.
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