The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice.
The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice.
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DOI：
10.1084/jem.20022125
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发表时间：
2003-07-07
期刊：
影响因子：
--
通讯作者：
Sayegh MH
中科院分区：
文献类型：
--
作者：
Ansari MJ;Salama AD;Chitnis T;Smith RN;Yagita H;Akiba H;Yamazaki T;Azuma M;Iwai H;Khoury SJ;Auchincloss H Jr;Sayegh MH
程序性死亡-1 （PD-1）受体是一种在活化T细胞上发现的抑制性共刺激分子，已被证明在免疫反应和外周耐受的调节中发挥作用。我们研究了这一途径在自身免疫性糖尿病发展中的作用。PD-1或PD-L1阻断而非PD-L2阻断在糖尿病前期雌性非肥胖糖尿病（NOD）小鼠（不论年龄（1至10周龄））中迅速沉淀糖尿病，尽管在老年小鼠中最明显。相比之下，细胞毒性T淋巴细胞相关抗原4 （CTLA-4）阻断仅在新生儿中诱导疾病。在PD-1-PD-L1通路阻断后，雄性NOD小鼠也发生了糖尿病，而NOD基因同源但对糖尿病发展有抵抗力的NOR小鼠则没有发生糖尿病。与对照组相比，PD-1-PD-L1通路阻断后，胰岛素评分显著升高，产生干扰素γ γ的gad反应性脾细胞频率增加。有趣的是，NOD小鼠炎症胰岛上发现PD-L1而非PD-L2表达。这些数据证明了PD-1-PD-L1相互作用在NOD小鼠自身免疫性糖尿病诱导和进展的调节中的核心作用，并为开发针对该疾病的这种共刺激途径的新疗法提供了理论依据。
Programmed death-1 (PD-1) receptor, an inhibitory costimulatory molecule found on activated T cells, has been demonstrated to play a role in the regulation of immune responses and peripheral tolerance. We investigated the role of this pathway in the development of autoimmune diabetes. PD-1 or PD-L1 but not PD-L2 blockade rapidly precipitated diabetes in prediabetic female nonobese diabetic (NOD) mice regardless of age (from 1 to 10-wk-old), although it was most pronounced in the older mice. By contrast, cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) blockade induced disease only in neonates. Male NOD mice also developed diabetes after PD-1–PD-L1 pathway blockade, but NOR mice, congenic to NOD but resistant to the development of diabetes, did not. Insulitis scores were significantly higher and frequency of interferon γ–producing GAD-reactive splenocytes was increased after PD-1–PD-L1 pathway blockade compared with controls. Interestingly, PD-L1 but not PD-L2 was found to be expressed on inflamed islets of NOD mice. These data demonstrate a central role for PD-1–PD-L1 interaction in the regulation of induction and progression of autoimmune diabetes in the NOD mouse and provide the rationale to develop new therapies to target this costimulatory pathway in this disease.
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影响因子：
30.5
作者：
Latchman, Y;Wood, CR;Freeman, GJ
通讯作者：
Freeman, GJ
DOI：
10.1084/jem.193.7.839
发表时间：
2001-04-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Tseng SY;Otsuji M;Gorski K;Huang X;Slansky JE;Pai SI;Shalabi A;Shin T;Pardoll DM;Tsuchiya H
通讯作者：
Tsuchiya H
影响因子：
2.4
作者：
Eppihimer, MJ;Gunn, J;Leonard, JP
通讯作者：
Leonard, JP
影响因子：
158.5
作者：
Herold, KC;Hagopian, W;Bluestone, JA
通讯作者：
Bluestone, JA
影响因子：
32.4
作者：
Nishimura, H;Nose, M;Honjo, T
通讯作者：
Honjo, T