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Blood, 15 June 2006, Vol. 107, No. 12, pp. 4817-4824.
Prepublished online as a Blood First Edition Paper on February 21, 2006; DOI 10.1182/blood-2006-01-0057.


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IMMUNOBIOLOGY

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

Jennifer L. Chan, Katherine C. Tang, Anoop P. Patel, Larissa M. Bonilla, Nicola Pierobon, Nicholas M. Ponzio, and Pranela Rameshwar

From the Graduate School of Biomedical Sciences, the Department of Pharmacology and Physiology, the Department of Pathology and Laboratory Medicine, and the Department of Medicine-Hematology/Oncology, New Jersey Medical School (NJMS)–University of Medicine and Dentistry of New Jersey (UMDNJ), Newark, NJ.

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 IFN{gamma}-knockdown MSCs and with anti–IFN{gamma} receptor confirmed that MHC-II expression requires autocrine stimulation by IFN{gamma}. During APC functions, as IFN{gamma} 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 IFN{gamma} 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 IFN{gamma} are required for MHC-II expression on MSCs, and for APC functions. APC functions occur during a narrow window before IFN{gamma} levels are increased. The study has implications for BM protection against infection and exacerbated inflammatory responses.


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