Coexpression of B7-1 and viral ("self") transgenes in pancreatic beta cells can break peripheral ignorance and lead to spontaneous autoimmune diabetes.
Coexpression of B7-1 and viral ("self") transgenes in pancreatic beta cells can break peripheral ignorance and lead to spontaneous autoimmune diabetes.
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B7-1 和病毒（“自身”）转基因在胰腺 β 细胞中的共表达可以打破外周无知并导致自发性自身免疫性糖尿病。
DOI：
10.1016/1074-7613(95)90062-4
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发表时间：
1995
期刊：
影响因子：
32.4
通讯作者：
Oldstone,MB
中科院分区：
文献类型：
--
作者：
vonHerrath,MG;Guerder,S;Lewicki,H;Flavell,RA;Oldstone,MB
本研究以胰腺j3细胞表达淋巴细胞性脉络丛脑膜炎病毒（LCMV）糖蛋白（GP）或核蛋白（NP）作为自身抗原的转基因小鼠为模型，观察了共刺激分子87- 1在克服外周无知中的作用。单独的病毒转基因或87- 1不诱导自身免疫性糖尿病（IDDM）。而在表达87- 1和LCMV-GP的转基因小鼠中，抗自身（病毒）细胞毒性T淋巴细胞（CTL）被激活而无病毒感染，并发生自发性IDDM。相反，胸腺表达自身（病毒-NP）抗原的双基因RIP-B7-1 x RIP-NP小鼠删除了大部分自身反应性CTL，并且没有发展成自发性IDDM。然而，这些小鼠在LCMV感染后14天发生快速发病的IDDM，而单转基因RIP-NP小鼠仅在4-5个月内发生IDDM。快速IDDM与增加的抗自身CTL数量和由胰岛炎性淋巴细胞产生的IFN γ的优势相关，而患有缓慢发病的IDDM的单转基因RIP-NP同窝仔在胰腺浸润中显示较少的抗自身CTL和较多的IL+和IL-10产生T淋巴细胞。
We evaluated the role of the costimulatory molecule 87-l in overcoming perlpheral Ignorance in transgenic mice, which expressed the glycoprotein(GP) or nucleoproteln (NP) of lymphocytic choriomeningltls virus (LCMV) as the self-antigen in pancreatic j3 cells. The viral transgenes or 87-l alone did not induce autoimmune diabetes (IDDM). However, in blgenic mice expressing 87-l and LCMV-GP, anti-self (viral) cytotoxic T lymphocytes (CTL) were activated without viral infection and spontaneous IDDM occurred. In contrast, bigenic RIP-B7-1 x RIP-NP mice with thymlc expression of the self (viral-NP) antlgen deleted the majority of their autoreactlve CTL and did not develop spontaneous IDDM. However, these mice developed fastonset IDDM 14 days after LCMV infection, whereassingle-transgenlc RIP-NP llttermates developed IDDM only within 4-5 months. Rapid IDDM was associated with Increased numbers of ant&elf CTL and a predominance of IFNy produced by islet-inflltratlng lymphocytes, whereas single transgenic RIP-NP littermates with slow-onset IDDM displayed less anti-self CTL and more IL+ and IL-lO-producing T lymphocytes in pancreatic infiltrates.