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

Interferon-gamma has been shown to be important for the resolution of inflammation associated with CNS autoimmunity. Because one of the roles of gammadelta T cells is the regulation of inflammation, we asked whether gammadelta T cells were able to regulate CNS inflammation using the autoimmune disease mouse model experimental autoimmune encephalomyelitis (EAE). We show that the presence of gammadelta T cells was needed to promote the production of IFN-gamma 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 gammadelta T cells to produce IFN-gamma, and was specific to T cells in the CNS, as no alterations in IFN-gamma production were detectable in gammadelta T cell-deficient mice in the spleen and lymph nodes of mice with EAE or following immunization. Analysis of TCRgammadelta gene usage in the CNS showed that the only TCRdelta 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-gamma-producing cells in the CNS are the encephalitogenic T cells, and that gammadelta T 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-gamma-deficient mice. These data suggest that CNS resident gammadelta T cells promote the production of IFN-gamma by encephalitogenic T cells in the CNS, which is ultimately required for the recovery from EAE.