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

被引:319
作者
Kent, SC
Chen, YH
Bregoli, L
Clemmings, SM
Kenyon, NS
Ricordi, C
Hering, BJ
Hafler, DA [1 ]
机构
[1] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Boston, MA 02115 USA
[3] Univ Minnesota, Dept Surg, Diabet Inst Immunol & Transplantat, Minneapolis, MN 55455 USA
[4] Univ Miami, Diabet Res Inst, Cell Transplant Ctr, Miami, FL 33136 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1038/nature03625
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
In autoimmune type 1 diabetes, pathogenic T lymphocytes are associated with the specific destruction of insulin-producing beta-islet cells(1,2). 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(3). 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(4), 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.
引用
收藏
页码:224 / 228
页数:5
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