Protective DNA Vaccination Against MOG(91‐108)‐Induced Experimental Autoimmune Encephalomyelitis Involves Induction of IFNβ

Wefer, J.; Harris, R. A.; Lobell, A.

DNA vaccine coding for the encephalitogenic peptide MOG(91‐108) protects LEW.1AV1 from subsequent development of experimental autoimmune encephalomyelitis (EAE). Protection is associated with a type 1 immune response and is dependent on the presence of CpG DNA motifs. The mechanisms underlying the observed reduction of EAE development in protected rats have not been fully clarified. We investigated immunological characteristics of lymphocytes after DNA vaccinaton and subsequent EAE induction. We confirm that protection was not associated with suppression of T1 cells, as transcription of the novel molecule rat T‐cell immunoglobulin‐ and mucin‐domain‐containing molecule (TIM‐3), reported to be exclusively expressed on differentiated T1 cells, was not altered by DNA vaccination. We did not note any clonal deletion upon tolerization, but detected an antigen‐specific lymphocyte population upregulating IFNγ upon recall stimulation 3 weeks after protective DNA vaccination. In protected rats, we observed (1) no alterations in antigen‐specific Th2 or Th3 responses, (2) reduced MHC II expression on splenocytes early after EAE induction, (3) antigen‐specific upregulation of IFNβ upon recall stimulation and (4) reduced IL‐12Rβ2 on lymphocytes. We thus demonstrate an association of the protective effect of DNA vaccination with expression of IFNβ. We are currently investigating the cellular mechanisms behind this IFNβ‐mediated protection.