Local expression of TNFα in neonatal NOD mice promotes diabetes by enhancing presentation of islet antigens
Local expression of TNFα in neonatal NOD mice promotes diabetes by enhancing presentation of islet antigens
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DOI：
10.1016/s1074-7613(00)80670-6
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发表时间：
1998-11-01
期刊：
影响因子：
32.4
通讯作者：
Flavell, RA
中科院分区：
文献类型：
--
作者：
Green, EA;Eynon, EE;Flavell, RA
炎症与自身免疫的关系早已被观察到，但其潜在的机制尚不清楚。在这里，我们证明了胰岛特异性表达的肿瘤坏死因子α在新生非肥胖型糖尿病小鼠中加速了糖尿病。在新生转基因小鼠中，一些β细胞发生凋亡，残留的胰岛细胞表面MHC-I类分子表达上调，携带MHC-胰岛多肽复合体的抗原提呈细胞和T细胞同时内流和激活，从而导致疾病的发生。从新生儿胰岛中渗入树突状细胞/巨噬细胞，而不是B细胞，在体外激活胰岛特异性T细胞。因此，炎症可以通过招募和激活树突状细胞/巨噬细胞向自身反应性T细胞递送自身抗原来触发自身免疫。
The relationship of inflammation to autoimmunity has been long observed, but the underlying mechanisms are unclear. Here, we demonstrate that islet-specific expression of TNF alpha in neonatal nonobese diabetic mice accelerated diabetes. In neonatal transgenic mice, disease was preceded by apoptosis of some beta cells, upregulation of MHC class I molecules on residual islet cells, and influx and activation of both antigen-presenting cells bearing MHC-islet peptide complexes and T cells. Infiltrating dendritic cells/macrophages, but not B cells, from neonatal islets activated islet-specific T cells in vitro. Thus, inflammation can trigger autoimmunity by recruiting and activating dendritic cells/macrophages to present self-antigens to autoreactive T cells.