Antigen-presenting property of mesenchymal stem cells occurs during a narrow window at low levels of interferon-γ

Mesenchymal stem cells (MSCs) are mostly found around the vasculature system of the adult bone marrow (BM). They function as immune suppressors, express MHC-II, are phagocytic, and support T-cell cytotoxicity. We hypothesize that these contradictory properties of MSCs are important for BM homeostasi...

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Bibliographic Details
Published in:Blood 2006-06, Vol.107 (12), p.4817-4824
Main Authors: Chan, Jennifer L., Tang, Katherine C., Patel, Anoop P., Bonilla, Larissa M., Pierobon, Nicola, Ponzio, Nicholas M., Rameshwar, Pranela
Format: Article
Language:English
Subjects:
Antigen Presentation - immunology
Antigen-Presenting Cells - cytology
Antigen-Presenting Cells - immunology
Antigens, Fungal - immunology
Autocrine Communication - immunology
Biological and medical sciences
Bone Marrow - blood supply
Bone Marrow - immunology
Candida albicans - immunology
Candidiasis - immunology
CD4-Positive T-Lymphocytes - cytology
CD4-Positive T-Lymphocytes - immunology
Cells, Cultured
Flow Cytometry
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Gene Expression Regulation - immunology
Histocompatibility Antigens Class II - immunology
Humans
Immune Tolerance - immunology
Immunobiology
Inflammation - immunology
Interferon-gamma - immunology
Mesenchymal Stem Cells - cytology
Mesenchymal Stem Cells - immunology
Modulation of the immune response (stimulation, suppression)
Tetanus Toxoid - immunology
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Summary:Mesenchymal stem cells (MSCs) are mostly found around the vasculature system of the adult bone marrow (BM). They function as immune suppressors, express MHC-II, are phagocytic, and support T-cell cytotoxicity. We hypothesize that these contradictory properties of MSCs are important for BM homeostasis and occur partly through antigen presentation (antigen-presenting cells [APCs]) within a narrow window. Indeed, we have verified APC functions of MSCs to recall antigens, Candida albicans and Tetanus toxoid. The target cells have been identified to be CD4+ T cells. APC assays with IFNγ-knockdown MSCs and with anti–IFNγ receptor confirmed that MHC-II expression requires autocrine stimulation by IFNγ. During APC functions, as IFNγ levels become elevated, there was a concomitant decrease in MHC-II on MSCs. This observation was correlated with flow cytometry studies showing a gradual decrease in MHC-II expression as IFNγ levels were increased. The reduced levels of MHC-II correlated with losses in their allogeneic potential, as indicated in mixed lymphocyte reaction. In summary, endogenous and low levels of IFNγ are required for MHC-II expression on MSCs, and for APC functions. APC functions occur during a narrow window before IFNγ levels are increased. The study has implications for BM protection against infection and exacerbated inflammatory responses.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2006-01-0057