Dendritic cells (DCs) are the most important antigen presenting cells of the immune system; they are crucial for the initiation of T cell responses and also for inducing and maintaining tolerance to self-antigens. We developed SIN-lentivirus vectors which express specific antigens under transcriptional control of a DC specific promoter to induce antigen-specific tolerance in autoimmune disease. Upon infection of bone marrow derived hematopoietic stem cells the specific antigen is expressed only after the stem cells have differentiated into DCs, hence in the absence of inflammatory signals. We demonstrated the effectiveness of this strategy for inducing myelin oligodendrocyte glycoprotein (MOG)-specific tolerance in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. A patent application concerning this immuno-therapy strategy is currently under revision (No. PCT/EP2012/068954).
Funding: Swiss Multiple Sclerosis Society, “Forschungskredit” University of Zurich