Kurrer M O, Pakala S V, Hanson H L, Katz J D
Department of Pathology, Center for Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Proc Natl Acad Sci U S A. 1997 Jan 7;94(1):213-8. doi: 10.1073/pnas.94.1.213.
Insulin-dependent diabetes mellitus results from T cell-mediated destruction of insulin-producing, pancreatic islet beta cells. How this destruction takes place has remained elusive--largely due to the slow kinetics of disease progression. By crossing a transgenic mouse carrying a beta cell-specific T cell receptor onto the NOD.scid background, we produced a simplified but robust and accelerated model of diabetes. This mouse produces CD4+ T cells bearing transgenic T cell receptor but is devoid of CD8+ T cells and B cells. More importantly, this mouse develops a rapid diabetes, which has allowed us to record and quantify beta cell death. We have determined that beta cells within the inflamed islets die by apoptosis.
胰岛素依赖型糖尿病是由T细胞介导的、对产生胰岛素的胰岛β细胞的破坏所导致的。这种破坏是如何发生的一直难以捉摸，这主要是由于疾病进展的动力学较为缓慢。通过将携带β细胞特异性T细胞受体的转基因小鼠与NOD.scid背景小鼠杂交，我们构建了一个简化但强大且加速的糖尿病模型。这种小鼠产生携带转基因T细胞受体的CD4+ T细胞，但缺乏CD8+ T细胞和B细胞。更重要的是，这种小鼠会迅速患上糖尿病，这使我们能够记录并量化β细胞死亡情况。我们已经确定，炎症胰岛内的β细胞通过凋亡死亡。
