Bieg S, Bailyes E M, Yassin N, Amann J, Herberg L, McGregor A M, Scherbaum W A, Banga J P
Department of Internal Medicine, University Hospital Ulm, FRG.
Diabetologia. 1993 May;36(5):385-90. doi: 10.1007/BF00402272.
Type 1 (insulin-dependent) diabetes mellitus is a T-cell mediated autoimmune disease with a number of different proteins being implicated as target autoantigens. A 38 kDa protein residing in the insulin secretory granule of insulinoma tissue is recognized by T-cell clones from a newly-diagnosed Type 1 diabetic patient. We have investigated the capacity of normal rat pancreatic beta-cell extracts and various subcellular fractions of transplantable RIN tissue to induce proliferation of T cells from non-obese diabetic (NOD) mice and H-2 identical NON.NOD-H-2g7 control mice. Normal rat islet beta-cell protein fractions induced intense, dose-dependent proliferation of NOD splenic T cells, but only marginal proliferative responses of NON.NOD-H-2g7 splenic T cells. To further localize the target antigens, four different subcellular fractions from RIN tissue were used as a source of antigen; here in particular the cytosolic proteins showed dose-dependent activation capacity with splenic T cells in NOD animals. These activities were absent in control mice. There was no proliferation after incubation with microsome preparations from other rat endocrine tissues. Purified carboxypeptidase H did not have any stimulatory activity on NOD T cells. Fractionation of the RIN cytosolic proteins showed a large number of different fractions eliciting proliferative activity. These results demonstrate that NOD T cells respond to a large number of potential islet beta-cell target antigens and it will be necessary to utilize NOD T-cell clones to identify the number and nature of these antigens.
1型（胰岛素依赖型）糖尿病是一种由T细胞介导的自身免疫性疾病，有多种不同蛋白质被认为是靶自身抗原。一种存在于胰岛素瘤组织胰岛素分泌颗粒中的38 kDa蛋白质可被一名新诊断的1型糖尿病患者的T细胞克隆识别。我们研究了正常大鼠胰腺β细胞提取物以及可移植的RIN组织的各种亚细胞组分诱导非肥胖糖尿病（NOD）小鼠和H-2相同的NON.NOD-H-2g7对照小鼠T细胞增殖的能力。正常大鼠胰岛β细胞蛋白质组分诱导NOD脾T细胞强烈的、剂量依赖性增殖，但仅诱导NON.NOD-H-2g7脾T细胞产生微弱的增殖反应。为了进一步定位靶抗原，使用RIN组织的四种不同亚细胞组分作为抗原来源；在此，特别是胞质蛋白对NOD动物的脾T细胞显示出剂量依赖性激活能力。对照小鼠中不存在这些活性。与来自其他大鼠内分泌组织的微粒体制剂孵育后没有增殖。纯化的羧肽酶H对NOD T细胞没有任何刺激活性。RIN胞质蛋白的分级分离显示大量不同组分具有增殖活性。这些结果表明，NOD T细胞对大量潜在的胰岛β细胞靶抗原产生反应，利用NOD T细胞克隆来鉴定这些抗原的数量和性质将是必要的。
