Foulis Alan K
Department of Pathology, Royal Infirmary, Glasgow G4 OSF, UK.
Novartis Found Symp. 2008;292:2-13; discussion 13-8, 122-9, 202-3.
In type 1 autoimmune diabetes there is a selective destruction of insulin-secreting beta cells. Around the time of clinical presentation, insulitis, a chronic inflammatory infiltrate of the islets affecting primarily insulin containing islets, is present in the majority of cases. The inflammatory infiltrate consists primarily of T lymphocytes; CD8 cells outnumber CD4 cells, there are fewer B lymphocytes and macrophages are relatively scarce. beta cell death may involve the Fas apoptotic pathway since they have been shown to express Fas, infiltrating T lymphocytes express Fas-L and apoptotic beta cells have been described. Hyperexpression of class I MHC by all the endocrine cells in many insulin-containing islets is a well recognized phenomenon, characteristic of the disease. It has been argued that this is an earlier event than insulitis within a given islet and appears to be due to secretion of interferon alpha by beta cells within that islet. A recent study has found evidence of Coxsackie virus infection in beta cells in three out of six pancreases of patients with recent-onset type 1 diabetes. Coxsackie viruses are known to induce interferon alpha secretion by beta cells and this could initiate the sequence of events that culminates in their autoimmune destruction.
在1型自身免疫性糖尿病中，胰岛素分泌β细胞会被选择性破坏。在临床表现出现前后，大多数病例存在胰岛炎，即胰岛的慢性炎症浸润，主要影响含胰岛素的胰岛。炎症浸润主要由T淋巴细胞组成；CD8细胞数量超过CD4细胞，B淋巴细胞较少，巨噬细胞相对稀少。β细胞死亡可能涉及Fas凋亡途径，因为已证明它们表达Fas，浸润的T淋巴细胞表达Fas-L，且已描述了凋亡的β细胞。许多含胰岛素胰岛中的所有内分泌细胞I类MHC的过度表达是一种公认的现象，是该疾病的特征。有人认为，在给定的胰岛中，这是比胰岛炎更早发生的事件，似乎是由于该胰岛内的β细胞分泌α干扰素所致。最近一项研究发现，在近期发病的1型糖尿病患者的六个胰腺中有三个的β细胞中存在柯萨奇病毒感染的证据。已知柯萨奇病毒可诱导β细胞分泌α干扰素，这可能引发一系列最终导致其自身免疫性破坏的事件。
