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

J Gene Med. 2009 Nov;11(11):1064-70. doi: 10.1002/jgm.1387.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control*
  • Female
  • Immunosuppressive Agents / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Myelin Proteins
  • Myelin-Associated Glycoprotein / genetics
  • Myelin-Associated Glycoprotein / metabolism
  • Myelin-Oligodendrocyte Glycoprotein
  • Tacrolimus / pharmacology*
  • Vaccination
  • Vaccines, DNA / immunology*

Substances

  • Adjuvants, Immunologic
  • Immunosuppressive Agents
  • Mog protein, mouse
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • Vaccines, DNA
  • Tacrolimus