Accumulation of T-cells with selected T-cell receptors in the brains of Japanese encephalitis virus-infected mice.

Accumulation of T-cells with selected T-cell receptors in the brains of Japanese encephalitis virus-infected mice.
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DOI:
10.7883/yoken.jjid.2008.40
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发表时间:
2008-01
影响因子:
2.2
通讯作者:
Yoshiki Fujii;Kazutaka Kitaura;K. Nakamichi;T. Takasaki;R. Suzuki;I. Kurane
Yoshiki Fujii;Kazutaka Kitaura;K. Nakamichi;T. Takasaki;R. Suzuki;I. Kurane
中科院分区:
医学4区
文献类型:
--
作者:
Yoshiki Fujii;Kazutaka Kitaura;K. Nakamichi;T. Takasaki;R. Suzuki;I. Kurane

文献摘要

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日本脑炎是一种严重的中枢神经系统(CNS)疾病,人类病死率很高。我们在小鼠模型中表征了日本脑炎病毒 (JEV) 感染后浸润大脑的 T 细胞,并通过分析 T 细胞受体互补决定区 3 (CDR3) 的序列确定了浸润 T 细胞的克隆性。 C3H/He 小鼠在腹​​膜内感染 JEV JaTH160 株后死亡,表明 CNS 变性和显着的 T 细胞浸润。感染小鼠大脑浸润后,携带 VA5-1、VA17-1、VA19-1、VB2-1、VB8-3 和 VB13-1 亚家族的 T 细胞百分比显着增加。此外,CDR3 大小谱分析揭示了携带 VA11-1 和 VA18-1 的 T 细胞中的寡克隆性。然后确定 VA5-1、VA11-1、VA18-1、VB8-3 和 VB13-1 亚家族的 CDR3 氨基酸序列。这些T细胞中CDR3的氨基酸序列具有高度的同一性和相似性。实时定量PCR分析还显示,CD8、干扰素-γ和肿瘤坏死因子-α在受感染的小鼠大脑中高表达。这些结果表明,具有高克隆性和相似性的T细胞浸润到JEV感染的小鼠大脑中,并且这些T细胞主要是CD8阳性并具有Th1/Tc1表型。
Japanese encephalitis is a severe central nervous system (CNS) disease with a high case fatality rate in humans. We characterized T-cells infiltrating the brain after infection with Japanese encephalitis virus (JEV) in a mouse model and determined the clonality of the infiltrating T-cells by analyzing the sequences of complementary determining region 3 (CDR3) of the T-cell receptor. C3H/He mice died after intraperitoneal infection with the JaTH160 strain of JEV, demonstrating CNS degeneration and prominent T-cell infiltration. The percentages of T-cells bearing the VA5-1, VA17-1, VA19-1, VB2-1, VB8-3 and VB13-1 subfamilies were significantly increased following infiltration of the brains in infected mice. Additionally, CDR3 size spectratyping revealed the oligoclonality in T-cells bearing VA11-1 and VA18-1. CDR3 amino acid sequences were then determined for the VA5-1, VA11-1, VA18-1, VB8-3 and VB13-1 subfamilies. There were high levels of identity and similarity in amino acid sequences of CDR3 in these T-cells. Quantitative real-time PCR analysis also revealed that CD8, interferon-gamma and tumor necrosis factor-alpha were highly expressed in the infected mouse brain. These results indicate that T-cells with high clonality and similarity infiltrate the JEV-infected mouse brain, and that these T-cells are mainly CD8-positive and have the Th1/Tc1 phenotype.