Huang G C, Tremble J, Bailyes E, Arden S D, Kaye T, McGregor A M, Banga J P
Department of Medicine, King's College School of Medicine, London, UK.
Clin Exp Immunol. 1995 Oct;102(1):152-8. doi: 10.1111/j.1365-2249.1995.tb06649.x.
T cells reacting with pancreatic islet beta cell proteins play a pivotal role in the pathogenesis of type 1 diabetes in experimental animal models and man, although the islet cell autoantigens against which these T cells are directed remain to be characterized. We have previously shown the presence of disease-related antigens residing in the transplantable RIN insulinoma membranes which are recognized by T cells from diabetic NOD mice. We now report on the establishment of CD4+, T cell lines reacting with insulinoma membranes from six newly diagnosed type 1 diabetic patients. Detailed examination of T cell lines from two patients revealed that both the lines continued to react with normal islet cell proteins and, interestingly, were also stimulated by antigens present in brain microsomes. The two T cell lines showed reactivity with different molecular weight proteins of the insulinoma membranes and both the lines were histocompatibility-linked antigen (HLA)-DR restricted. Although the insulinoma membrane preparation is known to contain glutamic acid decarboxylase (GAD), none of the six T cell lines proliferates in response to purified GAD. These T cell lines will be valuable in characterizing novel islet beta cell antigens which are likely to be implicated in type 1 diabetes.
在实验动物模型和人类中，与胰岛β细胞蛋白发生反应的T细胞在1型糖尿病的发病机制中起着关键作用，尽管这些T细胞所针对的胰岛细胞自身抗原仍有待确定。我们之前已经表明，可移植的RIN胰岛素瘤膜中存在与疾病相关的抗原，这些抗原能被糖尿病NOD小鼠的T细胞识别。我们现在报告建立了与6名新诊断的1型糖尿病患者的胰岛素瘤膜发生反应的CD4⁺ T细胞系。对两名患者的T细胞系进行的详细检查显示，这两个细胞系都继续与正常胰岛细胞蛋白发生反应，有趣的是，它们也受到脑微粒体中存在的抗原的刺激。这两个T细胞系与胰岛素瘤膜中不同分子量的蛋白质发生反应，并且这两个细胞系都受组织相容性连锁抗原（HLA）-DR限制。尽管已知胰岛素瘤膜制剂中含有谷氨酸脱羧酶（GAD），但这6个T细胞系中没有一个对纯化的GAD产生增殖反应。这些T细胞系对于鉴定可能与1型糖尿病有关的新型胰岛β细胞抗原将具有重要价值。
