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 S Kenyon, Camillo Ricordi, Bernhard J. Hering, David A. Hafler

Research output: Contribution to journalArticle

313 Citations (Scopus)

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

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Epitopes
Type 1 Diabetes Mellitus
Lymph Nodes
Insulin
T-Lymphocytes
Autoantigens
Islets of Langerhans
Antigen Presentation
Drainage
Alleles
Antigens

ASJC Scopus subject areas

  • General

Cite this

Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope. / Kent, Sally C.; Chen, Yahua; Bregoli, Lisa; Clemmings, Sue M.; Kenyon, Norma S; Ricordi, Camillo; Hering, Bernhard J.; Hafler, David A.

In: Nature, Vol. 435, No. 7039, 12.05.2005, p. 224-228.

Research output: Contribution to journalArticle

Kent, SC, Chen, Y, Bregoli, L, Clemmings, SM, Kenyon, NS, Ricordi, C, Hering, BJ & Hafler, DA 2005, 'Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope', Nature, vol. 435, no. 7039, pp. 224-228. https://doi.org/10.1038/nature03625
Kent, Sally C. ; Chen, Yahua ; Bregoli, Lisa ; Clemmings, Sue M. ; Kenyon, Norma S ; Ricordi, Camillo ; Hering, Bernhard J. ; Hafler, David A. / Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope. In: Nature. 2005 ; Vol. 435, No. 7039. pp. 224-228.
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