Live imaging of peripheral T cell-DC interactions in the islets: An emerging axis of autoimmune infiltration (48.15)

Abstract

Abstract Defining processes of islet infiltration and destruction in Type 1 diabetes (T1D) is important for its prevention and preventing destruction of transplanted islets in diabetic individuals. We hypothesize that T1D onset and persistence is maintained by T cell-dendritic cell (DC) interactions in both the draining pancreatic lymph node (PLN) and the islets. In the steady-state, we found that intra-islet DCs are a uniform semi-mature population that constitutively take up β cell antigens in preparation for antigen presentation. Islet-antigen specific CD8 T cells activated in the PLN trafficked to the islets where they induced maturation of islet DCs. Leukocytic infiltration of the islets and islet DC maturation were dependent on IFN-γ production by T cells. Blockade of antigen processing following T cell activation in the PLN also blocked islet DC maturation but not islet infiltration. This suggests that the DCs require productive antigen-presenting interactions with T cells in the islets for maturation to occur. Through 2-photon imaging of the islets, we visualized sustained interactions of islet-antigen specific CD8 T cells with islet DCs and characterized features of cytotoxicity and dwell-time in this setting. Taken together, these data suggest that directed and synaptic delivery of IFN-γ to intra-islet DCs induces their maturation. This work was funded by the Larry L. Hillblom Foundation and the Juvenile Diabetes Research Foundation.