Antigen-presenting property of mesenchymal stem cells occurs during a narrow window at low levels of interferon-gamma.
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 IFNgamma-knockdown MSCs and with anti-IFNgamma receptor confirmed that MHC-II expression requires autocrine stimulation by IFNgamma. During APC functions, as IFNgamma 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 IFNgamma 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 IFNgamma are required for MHC-II expression on MSCs, and for APC functions. APC functions occur during a narrow window before IFNgamma levels are increased. The study has implications for BM protection against infection and exacerbated inflammatory responses.
Department of Pharmacology and Physiology, New Jersey Medical School-University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.
Jennifer L
JL
Chan
Katherine C
KC
Tang
Anoop P
AP
Patel
Larissa M
LM
Bonilla
Nicola
N
Pierobon
Nicholas M
NM
Ponzio
Pranela
P
Rameshwar
D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D000946:Antigens, Fungal / Q000276:immunology; D019898:Autocrine Communication / Q000276:immunology*; D001853:Bone Marrow / Q000098:blood supply / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002176:Candida albicans / Q000276:immunology; D002177:Candidiasis / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology
D000946:Antigens, Fungal; D000949:Histocompatibility Antigens Class II; D013745:Tetanus Toxoid; D007371:Interferon-gamma