Intermolecular antigen spreading occurs during the preclinical period of human type 1 diabetes
Intermolecular antigen spreading occurs during the preclinical period of human type 1 diabetes
复制标题
DOI：
10.4049/jimmunol.166.8.5265
复制
发表时间：
2001-04-15
影响因子：
4.4
通讯作者：
Palmer, JP
中科院分区：
文献类型：
--
作者：
Brooks-Worrell, B;Gersuk, VH;Palmer, JP
T细胞对自身抗原反应的分子内和分子间扩散与自身免疫性疾病的发病机制有关。因此，我们质疑被确定为I型糖尿病（一种细胞介导的自身免疫性疾病）发展的高危受试者（自身抗体对胰岛蛋白反应阳性）的T细胞反应是否会显示T细胞对胰岛细胞蛋白反应的分子间Ag扩散。先前，我们已经证明，当受试者发展为I型糖尿病时，他们对许多胰岛蛋白有T细胞反应，而正常对照的T细胞对有限数量的胰岛蛋白有反应。对25名非糖尿病高危受试者的PBMC反应的初步测试表明，25名受试者中有16名对胰岛蛋白有类似于对照组的PBMC反应。这16名受试者中有14名可随访。14人中有11人对胰岛蛋白数量的增加产生了T细胞反应，其中6人患上了I型糖尿病。在最初就诊时已经表现出T细胞Ag扩散的9名受试者中，有4名可进行随访。在这四种中，有两种对胰岛蛋白的T细胞反应性有所增加，而另外两种则保持了它们最初的T细胞反应性水平。我们还观察到，在18名可随访的高危受试者中，有9人的自身抗体对胰岛蛋白的反应性中Ag扩散。我们的数据有力地支持了T细胞和Ab对胰岛蛋白反应的分子间扩散发生在I型糖尿病的临床前阶段的结论。
Intra- and intermolecular spreading of T cell responses to autoantigens has been implicated in the pathogenesis of autoimmune diseases. Therefore, we questioned whether T cell responses from subjects identified as at-risk (positive for autoantibody reactivity to islet proteins) for the development of type I diabetes, a cell-mediated autoimmune disease, would demonstrate intermolecular Ag spreading of T cell responses to islet cell proteins. Previously, we have demonstrated that by the time subjects develop type I diabetes, they have T cell responses to numerous islet proteins, whereas T cells from normal controls respond to a limited number of islet proteins. Initial testing of PBMC responses from 25 nondiabetic at-risk subjects demonstrated that 16 of the 25 subjects have PBMC responses to islet proteins similar to controls. Fourteen of these 16 subjects were available for follow-up. Eleven of the 14 developed T cell responses to increasing numbers of islet proteins, and 6 of these subjects developed type I diabetes. In the nine subjects who already demonstrated T cell Ag spreading at the initial visit, four were available for follow-up. Of these four, two had increases in T cell reactivity to islet proteins, while two maintained their initial levels of T cell reactivity. We also observed Ag spreading in autoantibody reactivity to islet proteins in nine of the 18 at-risk subjects available for follow-up. Our data strongly support the conclusion that intermolecular spreading of T cell and Ab responses to islet proteins occurs during the preclinical period of type I diabetes.