TNF-α Receptor 1 (p55) on Islets Is Necessary for the Expression of LIGHT on Diabetogenic T Cells

Insulin-dependent diabetes mellitus results from T-cell-mediated destruction of pancreatic islet β cells. Both CD4 and CD8 T cells have been shown to be independently capable of β cell destruction. However, the mechanism of β cell destruction has remained elusive. It has previously been shown that the absence of TNF-α receptor 1 (p55) on the islets protected islets from CD4 T-cell-mediated destruction as long as the T cells did not have access to wild-type islets in vivo. Wild-type and TNF-α receptor 1 (p55) deficient islets induce similar levels of proliferation of BDC2.5 T cells. In this study, we demonstrate that islet TNF-α receptor 1 (p55) influences the expression of LIGHT (TNFSF-14), a TNF family member with both cytolytic and costimulatory properties, on BDC2.5 T cells and the expression of its receptor HVEM (TNFRSF-14) by islets, indicating a role for LIGHT–HVEM interactions in autoimmune diabetes.