TNF-alpha 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 beta cells. Both CD4 and CD8 T cells have been shown to be independently capable of beta cell destruction. However, the mechanism of beta cell destruction has remained elusive. It has previously been shown that the absence of TNF-alpha 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-alpha receptor 1 (p55) deficient islets induce similar levels of proliferation of BDC2.5 T cells. In this study, we demonstrate that islet TNF-alpha 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.
Pakala
S V
SV
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Ilic
A
A
Chen
L
L
Sarvetnick
N
N
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000276:immunology*; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*
D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha