Activation of microglia and astrocytes in experimental autoimmune encephalitis (EAE) has been associated with chemokine induction in the CNS resulting in attraction of inflammatory infiltrate. The role of IL-17 in autoimmune disease has called into question the role of IFN-γ in EAE. In this report we investigate the necessity of IFN-γ receptor signaling in disease induction. To test this we made IFN-γR−/− radiation bone chimeras with animals expressing IFN-γR in the CNS, animals deficient for IFN-γR in the CNS but able to signal in the periphery and a wild-type control (WT). We found IFN-γR expression on astrocytes and microglia was critical for clinical disease symptoms in the adoptive transfer model of EAE. Without IFN-γ activation in the CNS there were no infiltrating leukocytes while in WT and in animals capable of signaling in the CNS there were CD4, CD8, and CD11b infiltrating cells. CCL2, CCL5 and CXCL10 were significantly decreased in CNS homogenates of animals devoid of IFN-γR on astrocytes and microglia compared to WT and mice expressing IFN-γR on peripheral leukocytes. These results argue that IFN-γ activation in the CNS is essential for clinical EAE disease induction.

Supported by NIH R01 NS034510.