Mesenchymal stromal cells cross-present soluble exogenous antigens as part of their antigen-presenting cell properties.
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.
François
Moïra
M
Department of Medicine and Oncology, Sir Mortimer B. Davis Jewish General Hospital & Lady Davis Institute for Medical Research, Montreal, QC, Canada.
Romieu-Mourez
Raphaëlle
R
Stock-Martineau
Sophie
S
Boivin
Marie-Noëlle
MN
Bramson
Jonathan L
JL
Galipeau
Jacques
J
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D000941:Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D045142:Cross-Priming / Q000276:immunology*; D005260:Female; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D012995:Solubility; D017154:Stromal Cells / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology; D001613:beta 2-Microglobulin / Q000235:genetics
D000941:Antigens; D016212:Transforming Growth Factor beta; D001613:beta 2-Microglobulin; D010047:Ovalbumin