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

Sally C. Kent, Yahua Chen, Lisa Bregoli, Sue M. Clemmings, Norma Sue Kenyon, Camillo Ricordi, Bernhard J. Hering, David A. Hafler

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)224-228
Number of pages5
JournalNature
Volume435
Issue number7039
DOIs
StatePublished - May 12 2005

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Cite this

Kent, S. C., Chen, Y., Bregoli, L., Clemmings, S. M., Kenyon, N. S., Ricordi, C., Hering, B. J., & Hafler, D. A. (2005). Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope. Nature, 435(7039), 224-228. https://doi.org/10.1038/nature03625