Analysis of islet inflammation in human type 1 diabetes
Analysis of islet inflammation in human type 1 diabetes
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DOI：
10.1111/j.1365-2249.2008.03860.x
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发表时间：
2009-02-01
影响因子：
4.6
通讯作者：
Morgan, N. G.
中科院分区：
文献类型：
--
作者：
Willcox, A.;Richardson, S. J.;Morgan, N. G.
1型糖尿病（T1D）的免疫病理学已被证明难以在人类中研究，因为合适的样本有限，但我们现在报告一项详细的研究，绘制人类T1D胰岛炎的演变。通过免疫组织化学分析了29例近期发病的T1D患者（平均年龄11.7岁）尸检后取出的胰腺样本。与胰岛胰岛素含量平行测定构成胰岛内炎性浸润（胰岛炎）的细胞类型。CD8（+）细胞毒性T细胞在胰岛炎中数量最多。巨噬细胞（CD68（+））也出现在早期和晚期胰岛炎，虽然在较少的数字。CD20（+）细胞在早期胰岛炎中仅少量存在，但随着β细胞死亡的进展，CD20（+）细胞被募集到胰岛。CD138（+）浆细胞在胰岛炎的各个阶段都很少见。所有患者的胰岛浸润中均存在CD4（+）细胞，但其丰度低于CD8（+）或CD68（+）细胞。叉头盒蛋白P3（+）调节性T细胞仅在单个患者的胰岛中检测到。即使在严重发炎的胰岛中，也很少检测到自然杀伤细胞。结果表明在人T1D中免疫细胞募集的确定序列。这意味着CD8（+）细胞毒性细胞和巨噬细胞都可能导致胰岛炎早期β细胞死亡。CD20（+）细胞在晚期胰岛炎中募集最多，表明随着胰岛炎的发展，这些细胞的作用越来越大。自然杀伤细胞和叉头盒蛋白P3（+）T细胞似乎不是β细胞死亡所必需的。
The immunopathology of type 1 diabetes (T1D) has proved difficult to study in man because of the limited availability of appropriate samples, but we now report a detailed study charting the evolution of insulitis in human T1D. Pancreas samples removed post-mortem from 29 patients (mean age 11.7 years) with recent-onset T1D were analysed by immunohistochemistry. The cell types constituting the inflammatory infiltrate within islets (insulitis) were determined in parallel with islet insulin content. CD8(+) cytotoxic T cells were the most abundant population during insulitis. Macrophages (CD68(+)) were also present during both early and later insulitis, although in fewer numbers. CD20(+) cells were present in only small numbers in early insulitis but were recruited to islets as beta cell death progressed. CD138(+) plasma cells were infrequent at all stages of insulitis. CD4(+) cells were present in the islet infiltrate in all patients but were less abundant than CD8(+) or CD68(+) cells. Forkhead box protein P3(+) regulatory T cells were detected in the islets of only a single patient. Natural killer cells were detected rarely, even in heavily inflamed islets. The results suggest a defined sequence of immune cell recruitment in human T1D. They imply that both CD8(+) cytotoxic cells and macrophages may contribute to beta cell death during early insulitis. CD20(+) cells are recruited in greatest numbers during late insulitis, suggesting an increasing role for these cells as insulitis develops. Natural killer cells and forkhead box protein P3(+) T cells do not appear to be required for beta cell death.