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. 2009 Sep 24;114(13):2632-8.
doi: 10.1182/blood-2009-02-207795. Epub 2009 Aug 4.

Mesenchymal stromal cells cross-present soluble exogenous antigens as part of their antigen-presenting cell properties

Moïra François  1 , Raphaëlle Romieu-Mourez, Sophie Stock-Martineau, Marie-Noëlle Boivin, Jonathan L Bramson, Jacques Galipeau
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Free article

Mesenchymal stromal cells cross-present soluble exogenous antigens as part of their antigen-presenting cell properties

Moïra François et al. Blood. .
Free article

Abstract

Recent studies involving bone marrow mesenchymal stromal cells (MSCs) demonstrated that interferon (IFN)-gamma 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-gamma 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-gamma was inhibited by transforming growth factor-beta, the overall cross-presentation capacity of MSCs remained unchanged after transforming growth factor-beta treatment. These observations were validated in vivo by performing an immune reconstitution assay in beta(2)-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.

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