Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope

• Published in: Nature Vol. 435; no. 7039; pp. 224 - 228
• Main Authors: Chen, Yahua, Ricordi, Camillo, Clemmings, Sue M, Hafler, David A, Hering, Bernhard J, Kenyon, Norma Sue, Kent, Sally C, Bregoli, Lisa
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 12-05-2005; Nature Publishing Group
• Subjects: Alleles; Amino Acid Sequence; Autoimmune diseases; Biological and medical sciences; Case-Control Studies; Clone Cells - cytology; Clone Cells - immunology; Diabetes; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - pathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Epitopes, T-Lymphocyte - immunology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; HLA-DR Antigens - immunology; HLA-DRB1 Chains; Humans; Insulin; Insulin - immunology; Lymph nodes; Lymph Nodes - cytology; Lymph Nodes - immunology; Lymphocytes; Medical sciences; Molecular Sequence Data; Pancreas; Pancreas - immunology; Properties; Receptors, Antigen, T-Cell - chemistry; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - immunology; Substrate Specificity; T cells; T-Lymphocytes - cytology; T-Lymphocytes - immunology; United States; Endocrinopathy; Autoimmunity; Human; Immunopathology; Pancreatic hormone; Antigenic determinant; Lymph node; Type 1 diabetes; Pathogenesis; T-Lymphocyte; Autoimmune disease; Insulin
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature03625

In autoimmune type 1 diabetes, pathogenic T lymphocytes are associated with the specific destruction of insulin-producing β-islet cells. Identification of the autoantigens involved in triggering this process is a central question. Here we examined T cells from pancreatic draining lymph nodes, the site of islet-cell-specific self-antigen presentation. We cloned single T cells in a non-biased manner from pancreatic draining lymph nodes of subjects with type 1 diabetes and from non-diabetic controls. A high degree of T-cell clonal expansion was observed in pancreatic lymph nodes from long-term diabetic patients but not from control subjects. The oligoclonally expanded T cells from diabetic subjects with DR4, a susceptibility allele for type 1 diabetes, recognized the insulin A 1-15 epitope restricted by DR4. These results identify insulin-reactive, clonally expanded T cells from the site of autoinflammatory drainage in long-term type 1 diabetics, indicating that insulin may indeed be the target antigen causing autoimmune diabetes.