Cellular Immunotherapy for Multiple Sclerosis using Tolerogenic Dendritic Cells

Abstract

Multiple sclerosis (MS) is a chronic neuroinflammatory disorder with autoimmune components, including autoreactive T helper 1 (Th1) and T helper 17 (Th17) cells, and the deficiency in regulatory T cells (Tregs). There is no cure for MS and current therapies often have limited efficacy and side effect. Tolerogenic dendritic cells (Tol-DCs) have a crucial role in regulating the immune system and preventing autoimmunity. Tol-DCs have been suggested as a potential immunotherapy for MS due to their tolerogenic mechanisms. This study aimed to analyse the therapeutic effect of Tol-DCs and their tolerogenic mechanisms in animal models of MS, the experimental autoimmune encephalomyelitis (EAE) as well as the safety of Tol-DCs treatment in MS patients. The results illustrated that myelin oligodendrocyte glycoprotein (MOG) loaded-Tol-DCs (Tol-DCs-MOG) decreased the severity of EAE compared to unload-Tol-DCs and vehicle control. Moreover, Tol-DCs-MOG treatment led to inhibiting Th1 and Th17 cells and inducing Tregs in spleens of EAE mice compared to unload-Tol-DCs and vehicle control. Other results suggested that Tol-DCs-MOG were able to switch the immune response from Th1 to Th2 cells through inducing IL-4 secretion and decrease the level of IFN-𝛾 in lymph nodes of EAE mice. Moreover, no adverse effects were observed in MS patients after injection with autologous myelin peptides-loaded Tol-DCs during 24 weeks follow up. Therefore, antigen-specific Tol-DCs immunotherapy could be a promising safe and effective treatment for MS that lead to restoring immune tolerance through inducing Tregs and the response of Th2 cells as well as inhibiting Th1 and Th17 cells.