Interferon- –stimulated marrow stromal cells: a new type of nonhematopoietic antigen-presenting cell

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 describe here that primary MSCs derived from C57BL/6micebehaveasconditionalantigenpresenting cells (APCs) and can induce antigen-specific protective immunity. Interferon gamma (IFN )–treated C57BL/6 MSCs, but not unstimulated MSCs, cocultured with ovalbumin-specific major histocompatibility (MHC) class II–restricted hybridomas in the presence of soluble ovalbumin-induced significant production of interleukin-2 (IL-2) in an antigen dose-dependent manner (P < .005). IFN -treated MSCs could further activate in vitro ovalbumin-specific primary transgenic CD4 T cells. C57BL/6 MSCs, however, were unable to induce antigen cross-presentation via the MHC class I pathway. When syngeneic mice were immunized intraperitoneally with ovalbumin-pulsed IFN -treated MSCs, they developed antigenspecific cytotoxic CD8 T cells and became fullyprotected (10of10mice)againstovalbumin-expressing E.G7 tumors. Human MSCs were also studied for antigen-presenting functions. IFN -treated DR1-positive human MSCs, but not unstimulated human MSCs, induced significant production of IL-2 when cocultured with DR1-restricted influenzaspecific humanized T-cell hybridomas in the presence of purified influenza matrix protein 1. Taken together, our data strongly suggest that MSCs behave as conditional APCs in syngeneic immune responses. (Blood. 2006;107:2570-2577)