Cutting edge: merocytic dendritic cells break T cell tolerance to beta cell antigens in nonobese diabetic mouse diabetes.

Cutting edge: merocytic dendritic cells break T cell tolerance to beta cell antigens in nonobese diabetic mouse diabetes.
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DOI:
10.4049/jimmunol.1001398
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发表时间:
2010-08-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Janssen EM
Janssen EM
中科院分区:
其他
文献类型:
--
作者:
Katz JD;Ondr JK;Opoka RJ;Garcia Z;Janssen EM

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在1型糖尿病(T1D)中,中枢和外周耐受性的破坏导致自身反应性T细胞破坏产生胰岛素的胰腺β细胞。在此,我们鉴定了负责介导胰岛抗原向CD8+ T细胞的交叉呈递和β细胞抗原向CD4+ T细胞的直接呈递的树突状细胞的关键亚群。这些细胞,称为分叶状树突状细胞(mcDC),在非肥胖糖尿病(NOD)小鼠中数量更多,当抗原负载的救援CD8+ T细胞从外周无能和缺失,同时刺激胰岛反应性CD4+ T细胞。当从明显糖尿病NOD小鼠的胰腺淋巴结中纯化时,mcDC在体内打破外周T细胞对β细胞的耐受性,并在年轻NOD小鼠中诱导快速发作的T1D。因此,mcDC亚群似乎代表了长期寻求的APC,负责打破体内对β细胞抗原的外周耐受。
In type 1 diabetes (T1D), the breach of central and peripheral tolerance results in autoreactive T cells destroying insulin-producing, pancreatic beta cells. Herein, we identify a critical sub-population of dendritic cells responsible for mediating both the cross-presentation of islet antigen to CD8+ T cells and the direct presentation of beta cell antigen to CD4+ T cells. These cells, termed merocytic dendritic cells (mcDC), are more numerous in nonobese diabetic (NOD) mouse, and when antigen-loaded rescue CD8+ T cells from peripheral anergy and deletion, while stimulating islet-reactive CD4+ T cells. When purified from the pancreatic lymph nodes of overtly diabetic NOD mice, mcDC break peripheral T cell tolerance to beta cells in vivo and induce rapid onset T1D in young NOD mouse. Thus, the mcDC subset appears to represent the long-sought APC responsible for breaking peripheral tolerance to beta cell antigen in vivo.
通过在胰腺淋巴结中发育调节的胰岛细胞抗原的发育表现来启动自身免疫性糖尿病。
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