Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction

被引：616

作者：

Tang, Qizhi ^{[2
]}

Adams, Jason Y. ^{[1
]}

Penaranda, Cristina ^{[1
]}

Melli, Kristin ^{[2
]}

Piaggio, Eliane ^{[3
]}

Sgouroudis, Evridiki ^{[4
]}

Piccirillo, Ciriaco A. ^{[4
]}

Salomon, Benoit L. ^{[3
]}

Bluestone, Jeffrey A. ^{[1
]}

机构：

[1] Univ Calif San Francisco, Dept Med, UCSF Diabet Ctr, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Dept Med, Dept Surg, San Francisco, CA 94143 USA

[3] Univ Paris 06, Hop La Pitie Salpetriere, UMR 7087, CNRS, F-75005 Paris, France

[4] McGill Univ, Dept Microbiol & Immunol, Ctr Study Host Resistance, Montreal, PQ H3A 2B4, Canada

来源：

IMMUNITY | 2008年 / 28卷 / 05期

关键词：

D O I：

10.1016/j.immuni.2008.03.016

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：687 / 697

页数：11

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