Tumor necrosis factor-related apoptosis-inducing ligand and CD56 expression in patients with type 1 diabetes mellitus

Objectives: Our previous report showed that beta-cell antigen - specific CD56(+) T-cells and cytokine TRAIL mediate destruction of human pancreatic beta cells in vitro. To determine whether CD56 and TRAIL are present during islet cell destruction at the onset of clinical symptoms of type 1 diabetes mellitus (T1D), we studied cell marker and cytokine expression in the pancreatic islets of 2 children who died at presentation of acute-onset T1D and in T-cell lines derived from a group of children with new-onset T1D. Methods: TRAIL, CD56, and other T-cell markers and cytokine expression were studied using immunohistochemistry on pancreatic sections from 2 children with acute-onset T1D. TRAIL and CD56 expression was analyzed by flow cytometry in the antigen-activated T-cell lines derived from 29 children with new-onset T1D. Results: TRAIL(+), CD56(+), CD45RO(+), and CD3(+) cells were present in the islets of acute-onset T1D patients, while none were present in the normal islets. T-cell lines from new-onset T1D expressed TRAIL and CD56 in response to stimulation with beta-cell antigens GAD, IA-2 and insulin b chain. Conclusion: The presence of TRAIL and CD56 markers is part of the T-cell response repertoire in beta-cell destruction.