To understand the role of IFN-c signaling to astrocytes during the pathogenesis of CNS autoimmune disease, EAE was induced in transgenic mice expressing a signaling deficient dominant negative IFN-c receptor 1 specifically on astrocytes (GFAPcR1D mice) [18] . Peripheral activation of self reactive T cells in GFAPcR1D mice was similar to wt mice (data not shown). This is consistent with both the CNS restricted transgene expression in the GFAPcR1D mice as well as the similar T cell activation following peripheral immunization with a non-self antigen [18] . Following immunization the incidence of disease, initiation of clinical symptoms, and initial symptom progression were unaltered by the inability of astrocytes to respond to IFN-c ( Fig. 1A ; Table 1 ). In addition, neither immunized group exhibited clinical symptoms of atypical EAE associated with the absence of IFN-c [19] . However, clinical symptoms in GFAPcR1D mice began to diverge from wt mice at , day 12 post immunization (p.i.) prior to the peak of clinical disease. In both groups clinical disease peaked at , day 14 p.i., but severity was increased from a score of 3.1 in wt mice to 4.0 in the GFAPcR1D group ( Fig. 1A ; Table 1 ).