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 beta chain. CONCLUSION: The presence of TRAIL and CD56 markers is part of the T-cell response repertoire in beta-cell destruction.