Human leukocyte antigens of class-I (HLA-I) molecules are hyper-expressed in insulin-containing islets (ICI) of type 1 diabetic (T1D) donors. This study investigated the HLA-I expression in autoantibody positive (AAB+) donors and defined its intra-islet and intracellular localization as well as proximity to infiltrating CD8 T cells with high-resolution confocal microscopy. We found HLA-I hyper-expression had already occurred prior to clinical diagnosis of T1D in islets of AAB+ donors. Interestingly, throughout all stages of disease, HLA-I was mostly expressed by alpha cells. Hyper-expression in AAB+ and T1D donors was associated with intra-cellular accumulation in the Golgi. Proximity analysis showed a moderate but significant correlation between HLA-I and infiltrating CD8 T cells only in ICI of T1D donors, but not in AAB+ donors. These observations not only demonstrate a very early, islet-intrinsic immune-independent increase of HLA-I during diabetes pathogenesis, but also point towards a role for alpha cells in T1D.

I 类 (HLA-I) 分子的人类白细胞抗原在 1 型糖尿病 (T1D) 供体的含胰岛素胰岛 (ICI) 中过度表达。本研究调查了自身抗体阳性 (AAB+) 供体中的 HLA-I 表达，并通过高分辨率共聚焦显微镜确定了其胰岛内和细胞内定位以及与浸润 CD8 T 细胞的接近程度。我们发现在 AAB+ 供体胰岛临床诊断 T1D 之前，HLA-I 高表达已经发生。有趣的是，在疾病的所有阶段，HLA-I 主要由 α 细胞表达。AAB+ 和 T1D 供体的高表达与高尔基体的细胞内积累有关。接近分析显示，仅在 T1D 供体的 ICI 中，HLA-I 与浸润性 CD8 T 细胞之间存在中度但显着的相关性，而在 AAB+ 供体中则没有。