Flow cytometric analysis during chronic disease revealed an ,4fold increase in CD45 hi inflammatory cells confirming increased inflammation in the absence of IFN-c signaling to astrocytes (Fig. 8A ). Similar to the acute disease, relative percentages of neutrophils, macrophages, CD4 + and CD8 + T cells were all similar (Fig. 3) . Furthermore, no differences in expression of activation markers on CNS derived CD4 + T cells, including CD69, CD122, CD127, Fas, FasL, ICOS and CD152 were evident between the groups (data not shown). The percentages of MOG reactive Th1 cells were also not altered in the CNS of GFAPcR1D relative to wt mice (Fig. 8B ) and the decreased percentage of potentially destructive Th17 cells identified during acute disease (Fig 2) , was also sustained during chronic disease (Fig. 8B ). Equivalent expression of IL-7, IL-23 and TGF-b mRNA (Fig. 8C ) suggested that the decrease in Th17 cells was dependent upon an increase in IFN-c and not related to a defect in activation or maintenance signals [20] . Increased inflammation and sustained MHC class II expression on microglia (Fig. 8A ) further suggested that IFN-c signaling to astrocytes down regulates inflammation universally without altering the composition of the CNS infiltrates. This concept is supported by sustained composition of CNS infiltrates during inflammation induced astrocyte apoptosis [21] .