γδ T cell regulation of IFN-γ production by central nervous system-infiltrating encephalitogenic T cells: Correlation with recovery from experimental autoimmune encephalomyelitis

Interferon-γ has been shown to be important for the resolution of inflammation associated with CNS autoimmunity. Because one of the roles of γδ cells is the regulation of inflammation, we asked whether γδ cells were able to regulate CNS inflammation using the autoimmune disease mouse model experimental autoimmune encephalomyelitis (EAE). We show that the presence of γδ T cells was needed to promote the production of IFN-γ by both CD4 and CD8 T cells in the CNS before the onset of EAE. This regulation was shown to be independent of the ability of γδ T cells to produce IFN-γ, and was specific to T cells in the CNS, as no alterations in IFN-γ production were detectable in γδ T cell-deficient mice in the spleen and lymph nodes of mice with EAE or following immunization. Analysis of TCRγδ gene usage in the CNS showed that the only TCRδ V gene families present in the CNS before EAE onset are from the DV7s6 and DV105s1 gene families. We also show that the primary IFN-γ-producing cells in the CNS are the encephalitogenic T cells, and that γδ cell-deficient mice are unable to resolve EAE disease symptoms like control mice, thus exhibiting a long-term chronic disease course similar to that observed in IFN-γ-deficient mice. These data suggest that CNS resident γδ T cells promote the production of IFN-γ by encephalitogenic T cells in the CNS, which is ultimately required for the recovery from EAE.