Involvement of CD8+ T cells in the development of renal hemorrhage in a mouse model of hemorrhagic fever with renal syndrome
Involvement of CD8+ T cells in the development of renal hemorrhage in a mouse model of hemorrhagic fever with renal syndrome
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DOI：
10.1007/s00705-018-3786-x
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发表时间：
2018-02
影响因子：
2.7
通讯作者：
K. Shimizu;K. Yoshimatsu;Midori Taruishi;Yoshimi Tsuda;J. Arikawa
中科院分区：
文献类型：
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作者：
K. Shimizu;K. Yoshimatsu;Midori Taruishi;Yoshimi Tsuda;J. Arikawa
肾综合征出血热是由汉坦病毒感染引起的。虽然宿主免疫被认为参与了HFRS的发病机制，但其机制仍有待阐明。先前已经开发出一种HFRS小鼠模型，显示出与患者相似的肾出血。在本研究中，我们旨在阐明CD4+和CD8+T细胞是否参与小鼠肾出血模型的发展。在病毒接种前2天，6周龄BALB/c小鼠CD4+或CD8+T细胞被抗体耗尽。CD4+T细胞耗尽的小鼠出现了疾病的迹象，如短暂的体重减轻，皮毛皱褶和肾出血，与未耗尽的小鼠一样。相比之下，CD8+T细胞缺失的小鼠没有出现疾病迹象。在确定BALB/c小鼠病毒糖蛋白上的CTL表位后，使用MHC四聚体分析病毒特异性CTL的数量。病毒感染小鼠脾脏和肾脏中病毒特异性ctl的数量显著增加。然而，高致病性克隆感染小鼠的数量与低致病性克隆感染小鼠的数量相当。我们之前报道了在感染过程中，高致病性克隆比低致病性克隆在小鼠肾脏中的繁殖效率更高。因此，靶蛋白和效应蛋白数量的平衡可能对疾病结果很重要。总之，本研究表明CD8+T细胞参与了HFRS小鼠模型肾出血的发生。
Hemorrhagic fever with renal syndrome (HFRS) is caused by hantavirus infection. Although host immunity is thought to be involved in the pathogenesis of HFRS, the mechanism remains to be elucidated. A mouse model of HFRS, which showed renal hemorrhage similar to that seen in patients, has been developed previously. In this study, we aimed to clarify whether CD4+and CD8+T cells are involved in the development of renal hemorrhage in the mouse model. At 2 days before virus inoculation, CD4+or CD8+T cells in 6-week-old BALB/c mice were depleted by administration of antibodies. The CD4+T cell-depleted mice developed signs of disease such as transient weight loss, ruffled fur and renal hemorrhage as in non-depleted mice. In contrast, the CD8+T cell-depleted mice showed no signs of disease. After determination of CTL epitopes on the viral glycoprotein in BALB/c mice, the quantity of virus-specific CTLs was analyzed using an MHC tetramer. The quantity of virus-specific CTLs markedly increased in spleens and kidneys of virus-infected mice. However, the quantity in high-pathogenic clone-infected mice was comparable to that in low-pathogenic clone-infected mice. We previously reported that the high-pathogenic clone propagated more efficiently than the low-pathogenic clone in kidneys of mice during the course of infection. Therefore, there is a possibility that the balance between quantities of the target and effector is important for disease outcome. In conclusion, this study showed that CD8+T cells are involved in the development of renal hemorrhage in a mouse model of HFRS.