Mesenchymal stem cells (MSCs) have the capacity to participate in tissue repair and modulate immune responses, making them an attractive potential therapy for autoimmune diseases. In the autoimmune disease multiple sclerosis (MS), encephalitogenic T cells enter the central nervous system (CNS) and initiate an inflammatory cascade that destroys neuron-insulating myelin. Current therapies for MS are limited and do not target CNS repair. Dental pulp stem cells (DPSCs) are MSCs derived from cells of the neural crest and may therefore have particular therapeutic utility in degenerative disorders of the nervous system. However, the therapeutic capacity of DPSCs is little explored in the context of MS or its animal model, experimental autoimmune encephalomyelitis (EAE). Furthermore, little is known about the immunomodulatory properties of DPSCs in autoimmune settings. In this study we show that DPSCs isolated from multiple human donors are able to suppress symptoms of MOG-induced chronic EAE. DPSC treatment was shown to reduce the emergence of pathogenic Th17 cells and activation of B cells in the CNS. While inhibitory effects against Th17 cell differentiation are still under investigation, in vitro experiments revealed DPSCs potently suppress B cell differentiation and up-regulation of MHC-II. DPSC effects on B cells are mediated at least in part by secretory factors. Further investigation is currently aimed at identifying immunosuppressive factors expressed by DPSCs and the mechanism by which they constrain the pathogenic immune response in EAE.