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1型糖尿病患者胰岛β细胞被破坏与胰岛自身反应性T细胞之间的直接联系从未被证明,对诊断后的疾病进程也所知无几。最近美国科学家的研究第一次对此有了直接的证据。冷冻胰腺样本来自病程在1周到超过50年的45例死亡患者的遗体捐赠,14例非糖尿病患者对照样本,5例有自身抗体的非糖尿病患者样本,2例孕期糖尿病患者样本,以及6例2型糖尿病患者样本。系统检查样本的组织切片是否存在有足够胰岛素的β细胞、CD8阳性的胰岛病变和1型HLA过度表达。最后,对表达HLA-A2的样本的连续切片用四聚体染色法针对6种已知确定的与1型糖尿病有关的胰岛自身抗原进行CD8 T细胞反应性检查。在临床确诊后最长达8年的分组患者胰岛样本中单一和多种CD8 T细胞反应性都检测到了。1型糖尿病特有的1型HLA过度表达和胰岛炎等病理特征存在于一小部分病程很长的患者中。在受影响的器官中,胰岛病变持续存在,表现为不同程度的浸润和β细胞丢失。该研究为人体胰岛自身反应性提供了第一个直接证据并强调了发病历程的异质性和长期性。
The direct link between islet β-cell destruction and islet autoreactive T cells in patients with type 1 diabetes has never been demonstrated, and the course of the disease after diagnosis is poorly understood. For the first time, the research of American scientists has direct evidence to this. Frozen pancreas samples were donated from remains of 45 deaths with disease durations ranging from 1 week to more than 50 years, 14 non-diabetic control samples, 5 non-diabetic patients with autoantibodies, 2 gestational diabetes samples and 6 2 Type of diabetes patients samples. The tissue sections of the samples were systematically examined for the presence of sufficient beta cells in the insulin, CD8 positive islet lesions, and type 1 HLA overexpression. Finally, serial sections of HLA-A2-expressing samples were examined for tetrazine CD8 T cell reactivity against six known islet autoantigens associated with type 1 diabetes. Single and multiple CD8 T cell reactivities were detected in the islet samples from grouping patients up to 8 years after clinical diagnosis. Type 1 diabetes-specific HLA-1 overexpression and insulitis and other pathological features exist in a small part of the long duration of patients. In the affected organs, islet lesions persist, showing varying degrees of infiltration and loss of beta cells. The study provides the first direct evidence of the islet self-reactivity in humans and highlights the heterogeneity and long-term nature of the disease course.