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Mesenchymal stromal cells cross-present soluble exogenous antigens as part of their antigen-presenting cell properties.
- Source :
-
Blood [Blood] 2009 Sep 24; Vol. 114 (13), pp. 2632-8. Date of Electronic Publication: 2009 Aug 04. - Publication Year :
- 2009
-
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.
- Subjects :
- Animals
Antigen Presentation immunology
Antigen-Presenting Cells metabolism
Antigen-Presenting Cells physiology
CD8-Positive T-Lymphocytes immunology
Cells, Cultured
Female
Mesenchymal Stem Cells metabolism
Mesenchymal Stem Cells physiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Ovalbumin immunology
Solubility
Stromal Cells metabolism
Stromal Cells physiology
Transforming Growth Factor beta metabolism
Transforming Growth Factor beta physiology
beta 2-Microglobulin genetics
Antigen-Presenting Cells immunology
Antigens immunology
Cross-Priming immunology
Mesenchymal Stem Cells immunology
Stromal Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 114
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 19654411
- Full Text :
- https://doi.org/10.1182/blood-2009-02-207795