The exaggerated neuroinflammation in CD83ΔMG mice is also characterized by a shifted ratio between FoxP3+ Tregs and IFN-γ producing Th cells in the inflamed CNS. Interestingly, high doses of IFN-γ subvert the capacity of microglia to induce Tregs in vitro60. This effect is also sensitive to the level of MHC-II on the microglial surface, as higher MHC-II expression inversely correlates with the proportion of induced antigen-specific Tregs. We also observed an increased proportion of CD11c+/MHC-II+ microglia in CD83ΔMG mice, which, together with heightened Th1-responses, could account for the observed reduction of Tregs and worsened disease outcome. Although the role of IFN-γ for the pathogenesis of EAE is still disputed61, Th1 cells are equally capable of inducing paralytic symptoms upon adoptive transfer compared to Th17 cells62. Furthermore, a unique IFN-γ producing T cell population is present in spinal fluids of MS patients, which is specifically enriched for the expression of MMP963. This subset expresses the chemokine receptors CCR2 and CCR5, which respond to CCL2 and CCL4/5, respectively. CD83-deficient microglia express significantly more CCL2 and CCL5 during EAE, and we detected increased
