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Blood, 24 September 2009, Vol. 114, No. 13, pp. 2632-2638. Prepublished online as a Blood First Edition Paper on August 4, 2009; DOI 10.1182/blood-2009-02-207795. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2009-02-207795v1 114/13/2632    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 François, M. Articles by Galipeau, J. PubMed PubMed Citation Articles by François, M. Articles by Galipeau, J. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Mesenchymal stromal cells cross-present soluble exogenous antigens as part of their antigen-presenting cell properties Moïra François1,2, Raphaëlle Romieu-Mourez1, Sophie Stock-Martineau1, Marie-Noëlle Boivin1, Jonathan L. Bramson3, and Jacques Galipeau1,2,* 1 Department of Medicine and Oncology, Sir Mortimer B. Davis Jewish General Hospital & Lady Davis Institute for Medical Research, Montreal, QC; 2 Department of Experimental Medicine, McGill University, Montreal, QC; and 3 Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON Recent studies involving bone marrow mesenchymal stromal cells (MSCs) demonstrated that interferon (IFN)– stimulation induces major histocompatibility complex (MHC) class II–mediated antigen presentation in MSCs both in vitro and in vivo. Concordantly, we investigated the ability of MSCs to present extracellular antigen through their MHC class I molecules, a process known as cross-presentation. Using an in vitro antigen presentation assay, we demonstrated that murine MSCs can cross-present soluble ovalbumin (OVA) to naive CD8+ T cells from OT-I mice. Cross-presentation by MSC was proteasome dependent and partly dependent on transporter associated with antigen-processing molecules. Pretreatment of MSC with IFN- increased cross-presentation by up-regulating antigen processing and presentation. However, although the transcription of the transporter associated with antigen processing-1 molecules and the immunoproteasome subunit LMP2 induced by IFN- was inhibited by transforming growth factor-β, the overall cross-presentation capacity of MSCs remained unchanged after transforming growth factor-β treatment. These observations were validated in vivo by performing an immune reconstitution assay in β2-microglobulin–/– mice and show that OVA cross-presentation by MSCs induces the proliferation of naive OVA-specific CD8+ T cells. In conclusion, we demonstrate that MSCs can cross-present exogenous antigen and induce an effective CD8+ T-cell immune response, a property that could be exploited as a therapeutic cell-based immune biopharmaceutic for the treatment of cancer or infectious diseases. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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