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

The role of IFNγ-induced expression of MHC class II by endothelial cells in efficient T cell homing to pancreatic islets (#184)

Nicholas A Scott 1 2 , Yuxing Zhao 2 , Tom W Kay 1 2 , Helen E Thomas 1 2
  1. Department of Medicine, St Vincent’s Hospital, The University of Melbourne, Fitzroy, Victoria, Australia
  2. St Vincent's Institute, Fitzroy, VIC, Australia

Diabetogenic T cells infiltrate beta cells by first transmigrating through the micro capillaries residing close to or within the pancreatic islets.  The detailed mechanism of interactions between circulating T cells and endothelial cells (ECs) lining the blood vessel wall, however, remains unclear. Here we study the role of IFNγ in this process.  We demonstrated that adoptive transfer of beta cell specific CD4 T cells into mice lacking IFNγ receptor resulted in a homing defect and delayed disease onset. Interestingly, we observed that upon IFNγ stimulation, MHC class II, which is not constitutively expressed on ECs, was rapidly unregulated on ECs in islets cultured in vitro. This suggests MHC class II may also express on ECs in inflamed islets in vivo. Indeed, there was a strong positive correlation between MHC class II expression on the endothelium with the level of infiltration in the islets from prediabetic NOD mice and beta cell specific TCR transgenic NOD mice. However, MHC class II upregulation on ECs was not seen in NOD.IFNgR2 knockout mice, even those with heavily infiltrated islets. This demonstrates that IFNγ signaling is crucial for MHC class II expression on ECs, which may play an important role in efficient activation and transmigration of diabetogenic T cells into islets. Our current studies focus on the function of class II MHC on endothelial cells in the interactions between antigen specific CD4+ T cells and ECs, and the impact of this interaction on diapedesis of T cells through the capillary wall into islets during the development of type 1 diabetes.