Poster Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

Imaging the dynamics of progressive autoimmune insulitis in the NOD mouse model of type 1 diabetes (#159)

Dan Holmberg 1 , Lisbeth Hansen 1 , Anja Schmidt-Christensen 1
  1. EMV-Immunology, Lund University, Lund, Sweden

In order to visualize the dynamics and interactions of the cells involved in autoimmune-driven inflammation in type 1 diabetes we have adopted the anterior chamber of the eye (ACE) transplantation model to perform non-invasive imaging of leucocytes infiltrating the endocrine pancreas. As proof-of-principle we demonstrate that fluorescently labeled leukocyte subsets can be followed in the diabetes-prone NOD mouse model of T1D. We show that individual, ACE-transplanted islets can be longitudinally and repetitively imaged by stereomicroscopy and two-photon microscopy during initiation and progression of insulitis. We demonstrate that, in spite of the immune privileged status of the eye, the ACE-transplanted islets of Langerhans develop infiltration and beta-cell destruction, recapitulating the autoimmune insulitis of the pancreas, and exemplify this by analyzing reporter cell populations expressing green fluorescent protein under the Cd11c or Foxp3 promoters. We also provide evidence that differences in morphological appearance of subpopulations of infiltrating leucocytes can be correlated to their distinct dynamic behavior. Together, these findings demonstrate that the kinetics and dynamics of these key cellular components of autoimmune diabetes can be elucidated using this imaging platform f or single cell resolution, non-invasive and repetitive monitoring of the individual islets of Langerhans during the natural development of autoimmune insulitis.