Novel epitope begets a novel pathway in type 1 diabetes progression.

Novel epitope begets a novel pathway in type 1 diabetes progression.
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新的表位在 1 型糖尿病进展中产生了新的途径。

DOI:
10.1172/jci37125
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发表时间:
2008
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Frelinger,JeffreyA
Frelinger,JeffreyA
中科院分区:
--
文献类型:
--
作者:
Frelinger,JeffreyA

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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 β cell peptides has been demonstrated, but functional data regarding the role of these cells in T1D have been lacking. In this issue of theJCI, 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 β 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.
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