Figure 8.

Two autoimmune pathways. EAE development in the rhMOG/CFA model involves two distinct pathogenic mechanisms. The 100 % EAE incidence (see Fig. 7a) maps to the MHC class II/Caja-DRB*W1201-restricted activation of Th1 cells specific for MOG epitope 24–36. The signature cytokine of this pathway, which essentially replicates mouse EAE models, is IFN$\mathit{\gamma }$. Early blockade of IL-12/IL-23 with a mAb against IL-12p40 abrogates the activation of this pathway. The observation that the EAE initiation pathway is activated in rhMOG/IFA model indicates that the responsive Th1 cells may be antigen-experienced cells. The variable EAE onset maps to another pathogenic mechanism, namely the MHC class I/Caja-E-restricted activation of CTL specific for MOG epitope 40–48, which shares almost complete sequence similarity with an epitope from the major capsid protein of CMV. The signature cytokine of this pathway is IL-17A. The characteristics and specificity of the CTLs suggest that they originate from the effector memory T cells that keep CMV under control. We hypothesize that the variable activation of the latter pathway is induced by antigens released from white matter lesions induced by the former pathway.