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Prepublished online as a Blood First Edition Paper on December 27, 2002; DOI 10.1182/blood-2002-07-2104. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-07-2104v1 101/9/3722    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Krampera, M. Articles by Dazzi, F. Search for Related Content PubMed PubMed Citation Articles by Krampera, M. Articles by Dazzi, F. Related Collections Hematopoiesis and Stem Cells Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 May 2003, Vol. 101, No. 9, pp. 3722-3729 TRANSPLANTATION Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide Mauro Krampera, Sarah Glennie, Julian Dyson, Diane Scott, Ruthline Laylor, Elizabeth Simpson, and Francesco Dazzi From the Department of Immunology and Transplantation Biology, Imperial College Faculty of Medicine, Hammersmith Hospital, London, United Kingdom. Mesenchymal stem cells (MSCs) have been recently shown to inhibit T-cell proliferation to polyclonal stimuli. We characterized the effect of MSCs of bone marrow origin on the T-cell response of naive and memory T cells to their cognate antigenic epitopes. The immune response to murine male transplantation antigens, HY, was selected because the peptide identity and major histocompatibility complex (MHC) restriction of the immunodominant epitopes are known. C57BL/6 female mice immunized with male cells were the source of memory T cells, whereas C6 mice transgenic for HY-specific T-cell receptor provided naive T cells. Responder cells were stimulated in vitro with male spleen cells or HY peptides in the presence or absence of MSCs. MSCs inhibited HY-specific naive and memory T cells in a dose-dependent fashion and affected cell proliferation, cytotoxicity, and the number of interferon  (IFN-)-producing HY peptide-specific T cells. However, the MSC inhibitory effect did not selectively target antigen-reactive T cells. When MSCs were added to the T-cell cultures in a Transwell system or MSCs were replaced by MSC culture supernatant, the inhibitory activity was abrogated. T-cell reactivity was also restored if MSCs were removed from the cultures. The expression of MHC molecules and the presence in culture of antigen-presenting cells (APCs) or of CD4+/CD25+ regulatory T cells were not required for MSCs to inhibit. We conclude that MSCs inhibit naive and memory T-cell responses to their cognate antigens. Overall our data suggest that MSCs physically hinder T cells from the contact with APCs in a noncognate fashion. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. J. Weiss, J. K. Kolls, L. A. Ortiz, A. Panoskaltsis-Mortari, and D. J. Prockop Stem Cells and Cell Therapies in Lung Biology and Lung Diseases Proceedings of the ATS, July 15, 2008; 5(5): 637 - 667. [Full Text] [PDF] R. Atoui, D. Shum-Tim, and R. C.J. Chiu Myocardial regenerative therapy: immunologic basis for the potential "universal donor cells". Ann. Thorac. 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