Hantavirus-specific CD8+-T-cell responses in newborn mice persistently infected with Hantaan virus
Hantavirus-specific CD8+-T-cell responses in newborn mice persistently infected with Hantaan virus
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DOI：
10.1128/jvi.77.15.8408-8417.2003
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发表时间：
2003-08-01
影响因子：
5.4
通讯作者：
Arikawa, J
中科院分区：
文献类型：
--
作者：
Araki, K;Yoshimatsu, K;Arikawa, J
利用汉滩病毒（HTNA）在小鼠体内研究了病毒特异性CD 8（+）-T细胞应答与病毒持续存在的关系。我们首先建立了一种简单的方法，通过流式细胞术测量病毒特异性CD 8（+）T细胞的水平。接下来，为了产生持续HTNV感染的小鼠模型，在出生后24小时内用1或0.150%新生小鼠致死剂量的HTNV皮下接种新生小鼠。所有逃脱致死性感染的小鼠持续感染HTNV，直到病毒接种后至少30天，并且没有产生γ干扰素（IFN-γ）的病毒特异性CD 8（+）T细胞。随后，根据功能性病毒特异性CD 8（+）T细胞的出现，病毒从一些小鼠中被消除，所述功能性病毒特异性CD 8（+）T细胞具有产生IFN-γ和肿瘤坏死因子α（TNF-α）的能力并且具有细胞毒性活性。无论是否存在病毒，在所有小鼠中均检测到中和抗体。在感染后30天内发生的急性期，在病毒接种后第15天检测到产生IFN-γ的HTNV特异性CD 8（+）T细胞。然而，这些特异性CD 8（+）T细胞的TNF-α产生和细胞毒活性受损，HTNV未被清除。几乎所有这些特异性CD 8（+）T细胞在第18天消失。这些结果表明，功能性HTNV特异性CD 8（+）T细胞对HTNV的清除很重要。
The relationship between virus-specific CD8(+)-T-cell responses and viral persistence was studied in mice by using Hantaan virus (HTNA). We first established a simple method for measuring levels of virus-specific CD8(+) T cells by How cytometry. Next, to produce a mouse model of persistent HTNV infection, newborn mice were inoculated subcutaneously within 24 h of birth with 1 or 0.150% newborn mouse lethal dose of HTNV. All mice that escaped lethal infection were persistently infected with HTNV until at least 30 days after virus inoculation and had no virus-specific CD8(+) T cells producing gamma interferon (IFN-gamma). Subsequently, the virus was eliminated from some of the mice, depending on the appearance of functional virus-specific CD8(+) T cells, which have the ability to produce IFN-gamma and tumor necrosis factor alpha (TNF-alpha) and have cytotoxic activity. Neutralizing antibodies were detected in all mice, regardless of the presence or absence of virus. In the acute phase, which occurs within 30 days of infection, IFN-gamma-producing HTNV-specific CD8(+) T cells were detected on day 15 after virus inoculation. However, TNF-alpha production and the cytotoxic activity of these specific CD8(+) T cells were impaired and HTNV was not removed. Almost all of these specific CD8(+) T cells disappeared by day 18. These results suggest that functional HTNV-specific CD8(+) T cells are important for clearance of HTNV.