Fas stimulation results in selective islet infiltrate apoptosis in situ and reversal of diabetes.
Breakdown of peripheral T cell regulation due to defective antigen-activated apoptosis may lead to autoimmunity. In the nonobese diabetic (NOD) mouse model of type 1 diabetes mellitus, we have demonstrated defects in T cell activation and peripheral apoptosis. Stimulation of the Fas pathway by a Fas receptor agonist led to enhanced in vitro apoptosis and in vivo selective apoptosis of islet-infiltrating lymphocytes. Administration of the Fas agonist immediately after onset of diabetes led to reversal of diabetes in NOD mice. Inducing peripheral T cell apoptosis may be a potential method for reversal of autoimmune diabetes.
Dharnidharka
Vikas R
VR
Departments of Pediatrics and Pathology, University of Florida College of Medicine, Gainesville, Florida 32610, USA. vikasmd@ufl.edu
Van Patten
Yancy
Y
Bahjat
F Rena
FR
Clare-Salzler
Michael
M
D000818:Animals; D000942:Antigens, Bacterial / Q000494:pharmacology; D017209:Apoptosis; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology; D004768:Enterotoxins / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D015398:Signal Transduction / Q000187:drug effects; D018417:Th1 Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D019014:fas Receptor / Q000378:metabolism*
D000942:Antigens, Bacterial; D004768:Enterotoxins; D019014:fas Receptor; C031818:enterotoxin B, staphylococcal