Subsequent to peak disease severity the clinical symptoms in wt mice began a modest decline by day 16 p.i. (Fig. 1A ). By contrast, GFAPcR1D mice not only exhibited increased severity of clinical symptoms following day 14 p.i., but the continued disease escalation was associated with increased mortality ( Fig. 1A ; Table 1 ). Sustained morbidity and significant mortality in GFAPcR1D mice after day 30 p.i. implied a critical role for IFN-c induced astrocyte signaling in neuroprotection and limiting disability. A similar absence of clinical remission was found in a preliminary experiment comparing EAE SJL mice carrying the GFAPcR1D gene (data not shown). These data suggest that astrocyte responses to IFN-c are protective, irrespective of genetic background.