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


CONCLUSIONS
The presence of TRAIL and CD56 markers is part of the T-cell response repertoire in beta-cell destruction.
Cheung
Sze-shuen C
SS
Department of Pediatrics, Faculty of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada.
Metzger
Daniel L
DL
Wang
Xiaojie
X
Huang
Junqi
J
Tai
Joseph
J
Tingle
Aubrey J
AJ
Ou
Dawei
D
D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D015415:Biomarkers; D019002:CD56 Antigen / Q000378:metabolism*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D019002:CD56 Antigen; D008562:Membrane Glycoproteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma