Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope
Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope
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DOI：
10.1038/nature03625
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发表时间：
2005-05-12
期刊：
影响因子：
64.8
通讯作者：
Hafler, DA
中科院分区：
文献类型：
--
作者：
Kent, SC;Chen, YH;Hafler, DA
在自身免疫性1型糖尿病中，致病性T淋巴细胞与产生胰岛素的β-胰岛细胞的特异性破坏相关（1，2）。识别参与触发这一过程的自身抗原是一个中心问题。在这里，我们检查了来自胰腺引流淋巴结的T细胞，胰岛细胞特异性自身抗原呈递的部位（3）。我们从1型糖尿病受试者和非糖尿病对照者的胰腺引流淋巴结中以无偏倚的方式克隆了单个T细胞。在长期糖尿病患者的胰腺淋巴结中观察到高度的T细胞克隆性扩增，但在对照组中未观察到。来自具有DR 4（1型糖尿病的易感等位基因（4））的糖尿病受试者的寡克隆扩增的T细胞识别受DR 4限制的胰岛素A1 - 15表位。这些结果从长期1型糖尿病患者的自身炎症引流部位鉴定出胰岛素反应性克隆扩增的T细胞，表明胰岛素确实可能是导致自身免疫性糖尿病的靶抗原。
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.