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 antigen-specific 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-gamma 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.
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 antigen-specific 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-gamma 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.
Authors: Laura Northrup; Joshua O Sestak; Bradley P Sullivan; Sharadvi Thati; Brittany L Hartwell; Teruna J Siahaan; Charlotte M Vines; Cory Berkland Journal: AAPS J Date: 2014-10-09 Impact factor: 4.009