FK506 as an adjuvant of tolerogenic DNA vaccination for the prevention of experimental autoimmune encephalomyelitis

Background: DNA vaccination is a strategy that has been developed primarily to elicit protective immunity against infection and cancer. Methods: DNA vaccine was used, in conjunction with an immunosuppressant, to tolerize harmful autoimmunity. Results: Immunization of C57BL/6 mice with MOG_35-55, a myelin oligodendrocyte glycoprotein-derived peptide, and FK506 (Tacrolimus) as a tolerogenic adjuvant stimulated regulatory dendritic cells, induced antigenspecific regulatory T cells (Treg), and protected the animals from subsequent induction of experimental autoimmune encephalomyelitis (EAE). After EAE induction, there were fewer lymphocytes, including fewer T helper 17 cells, and more Treg infiltrating the spinal cord in the immunized mice compared to in control mice. Furthermore, at the peak of the EAE manifestation, CD4 T cells in the immunized mice showed decreased expression of interferon-γ and interleukin (IL)-17, but not IL-4, in treated mice. Conclusions: DNA vaccination, when applied with an immunosuppressant as adjuvant, can induce antigen-specific tolerance and prevent autoimmune disease.