A decisive bridge between innate immunity and the pathognomonic morphological characteristics of type 1 diabetes demonstrated by instillation of heat-inactivated bacteria in the pancreatic duct of rats

AIMS: Periductal inflammation and accumulation of granulocytes and monocytes in the periislet area and in the exocrine pancreas is observed within hours after instillation of heat-inactivated bacteria in the ductal compartment of the pancreas in healthy rats. The present investigation was undertaken to study how the acute inflammation developed over time. METHODS: Immunohistochemical evaluation of the immune response triggered by instillation of heat-inactivated bacteria in the ductal compartment in rats. RESULTS: After three weeks, the triggered inflammation had vanished and pancreases showed normal morphology. However, a distinct accumulation of both CD4+ and CD8+ T cells within and adjacent to affected islets was found in one-third of the rats instilled with heat-inactivated E. faecalis, mimicking the insulitis seen at onset of human T1D. As in T1D, this insulitis affected a minority of islets and only certain lobes of the pancreases. Notably, a fraction of the T cells expressed the CD103 antigen, mirroring the recently reported presence of tissue resident memory T cells in the insulitis in humans with recent onset T1D. CONCLUSIONS: The results presented unravel a previously unknown interplay between innate and acquired immunity in the formation of immunopathological events indistinguishable from those described in humans with recent onset T1D.