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 Blood, 15 March 2006, Vol. 107, No. 6, pp. 2570-2577.
Prepublished online as a Blood First Edition Paper on November 17, 2005; DOI 10.1182/blood-2005-07-2793.

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Submitted July 14, 2005
Accepted October 27, 2005

Interferon-{gamma}-stimulated marrow stromal cells: a new type of non-hematopoietic antigen presenting cell

John Stagg, Sandra Pommey, Nicoletta Eliopoulos, and Jacques Galipeau*

Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada
Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada; Division of Hematology/Oncology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada

* Corresponding author; email: jacques.galipeau{at}mcgill.ca.

Several studies have demonstrated that marrow stromal cells (MSCs) can suppress allogeneic T cell responses. However, the effect of MSCs on syngeneic immune responses has been largely overlooked. We here describe that primary MSCs derived from C57BL/6 mice behave as conditional antigen-presenting cells (APCs) and can induce antigen-specific protective immunity. IFN{gamma}-treated C57BL/6 MSCs, but not unstimulated MSCs, cocultured with ovalbumin-specific MHC class II restricted hybridomas in the presence of soluble ovalbumin induced significant production of IL-2 in an antigen dose-dependent manner (P<0.005). IFN{gamma}-treated MSCs could further activate in vitro ovalbumin-specific primary OT-II-derived CD4+ T cells. C57BL/6 MSCs were however unable to induce antigen cross-presentation via MHC class I pathway. When syngeneic mice were immunized intraperitoneally with ovalbumin-pulsed IFN{gamma}-treated MSCs, they developed antigen-specific cytotoxic CD8+ T cells and became fully protected (10 out of 10 mice) against ovalbumin-expressing E.G7 tumors. Human MSCs were also studied for antigen presenting functions. IFN{gamma}-treated DR1-positive human MSCs, but not unstimulated human MSCs, cocultured with DR1-restricted influenza-specific humanized T cell hybridomas in the presence of purified influenza matrix protein 1 induced significant production of IL-2. Taken together, our data strongly suggest that MSCs behave as conditional APCs in syngeneic immune responses.


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