Modulation of dendritic cell function by neuroantigen-specific CD8+ T cells (P4065)

Experimental autoimmune encephalomyelitis (EAE) studies have established that myelin reactive T cells contribute significantly to the pathology of multiple sclerosis (MS). While auto-reactive CD4+ T cells have long been considered to be pathogenic, the role of CD8+ T cells is relatively unknown. We previously showed that myelin oligodendrocyte glycoprotein-specific CD8+ T cells (MOG-CD8+) suppress EAE; however, the mechanism of disease suppression is not completely understood. Here we show that CD11c+ dendritic cells (DC) from MOG-CD8+ recipient mice are less efficient in priming naïve and in activating recall CD4+ T cell response as compared to control ovalbumin-CD8+ recipients. In response to lipopolysaccharide stimulation, DC from MOG-CD8+ recipients demonstrated an anti-inflammatory cytokine profile with significantly lower IL-12 but higher IL-10 secretion. This was also confirmed in CD8-/- mice where DC from MOG-immunized CD8-/- mice secreted higher levels of IL-12 as compared to wild-type mice. MOG-CD8+ transfer to naïve mice did not affect DC function indicating that DC modulation requires cognate antigen presentation. Kinetic studies revealed that DC were modulated prior to disease onset at day 7 and persisted until day 30 post CD8+ transfer. Overall, our data suggest that transfer of CNS-antigen specific CD8+ T cells modulates DC function and can be an important mechanism of maintaining peripheral tolerance.