Frelinger Jeffrey A
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina 27599-7290, USA.
J Clin Invest. 2008 Oct;118(10):3268-71. doi: 10.1172/JCI37125.
While CD8+ T cells are critical to diabetogenesis in NOD mice, evidence of their involvement in human type 1 diabetes (T1D) has been circumstantial. The existence of CD8+ T cells specific for beta cell peptides has been demonstrated, but functional data regarding the role of these cells in T1D have been lacking. In this issue of the JCI, Skowera et al. describe an unusual self-peptide epitope derived from the leader sequence of preproinsulin (PPI) and show that 50% of HLA-A2+ patients with new-onset T1D possessed circulating CD8+ T cells specific for this epitope, suggesting that PPI plays a critical role in the development of T1D (see the related article beginning on page 3390). They also report that beta cells upregulate PPI expression in the presence of high glucose levels, rendering these cells more susceptible to lysis and potentially accelerating disease. This suggests that interventions aimed at decreasing the PPI-specific CD8+ T cell response early after T1D diagnosis may be efficacious in ameliorating the disease process.
虽然CD8 + T细胞对NOD小鼠的糖尿病发生至关重要，但其参与人类1型糖尿病（T1D）的证据尚不确凿。已证实存在对β细胞肽具有特异性的CD8 + T细胞，但关于这些细胞在T1D中作用的功能数据一直缺乏。在本期《临床研究杂志》中，Skowera等人描述了一种源自胰岛素原前体（PPI）前导序列的异常自身肽表位，并表明50%的新发T1D HLA - A2 +患者拥有针对该表位的循环CD8 + T细胞，这表明PPI在T1D的发展中起关键作用（见第3390页开始的相关文章）。他们还报告说，在高葡萄糖水平存在的情况下，β细胞会上调PPI表达，使这些细胞更容易被裂解，并可能加速疾病进程。这表明在T1D诊断后早期旨在降低PPI特异性CD8 + T细胞反应的干预措施可能对改善疾病进程有效。
