Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction
Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction
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DOI：
10.1016/j.immuni.2008.03.016
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发表时间：
2008-05-01
期刊：
影响因子：
32.4
通讯作者：
Bluestone, Jeffrey A.
中科院分区：
文献类型：
--
作者：
Tang, Qizhi;Adams, Jason Y.;Bluestone, Jeffrey A.
研究非肥胖糖尿病小鼠糖尿病进展过程中CD4(+)效应T细胞(TJeff细胞)和CD4(+)Foxp3(+)调节性T细胞(Treg细胞)的动态变化，以确定Treg细胞和Treg细胞失衡是否参与1型糖尿病的发生发展。我们的结果显示，炎症胰岛中Treg细胞与Teff细胞的比率逐渐降低，但在胰腺淋巴结中则没有。胰岛内Treg细胞CD25和Bcl2表达减少，提示它们的减少是由于细胞凋亡增加所致。此外，给予低剂量的白介素2(IL-2)可促进Treg细胞存活，并保护小鼠免受糖尿病的侵袭。综上所述，这些结果表明，继发于IL-2产生缺陷的胰岛内Treg细胞功能障碍是非肥胖糖尿病小鼠自我耐受性进行性崩溃和糖尿病发展的根本原因。
The dynamics of CD4(+) effector T cells (Teff cells) and CD4(+)Foxp3(+) regulatory T cells (Treg cells) during diabetes progression in nonobese diabetic mice was investigated to determine whether an imbalance of Treg cells and Teff cells contributes to the development of type 1 diabetes. Our results demonstrated a progressive decrease in the Treg cell:Teff cell ratio in inflamed islets but not in pancreatic lymph nodes. Intra-islet Treg cells expressed reduced amounts of CD25 and Bcl-2, suggesting that their decline was due to increased apoptosis. Additionally, administration of low-dose interleukin-2 (IL-2) promoted Treg cell survival and protected mice from developing diabetes. Together, these results suggest intra-islet Treg cell dysfunction secondary to defective IL-2 production is a root cause of the progressive breakdown of self-tolerance and the development of diabetes in nonobese diabetic mice.