Hayasaka Daisuke, Maeda Ken, Ennis Francis A, Terajima Masanori
Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Virus Res. 2007 Feb;123(2):120-7. doi: 10.1016/j.virusres.2006.08.006. Epub 2006 Sep 18.
Hantavirus infection causes two human diseases, hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. The typical feature of these diseases is increased permeability in microvascular beds in the kidneys and the lungs, respectively. The mechanism of capillary leakage, however, is not understood. Some evidence suggests that hantavirus disease pathogenesis is immunologically mediated by cytotoxic T lymphocytes and other immune cells in target organs producing inflammatory cytokines. In this study we examined the roles of virus-specific cytotoxic T lymphocytes in increased permeability of human endothelial cells infected with hantavirus. We used a human CD8(+) hantavirus-specific cytotoxic T lymphocyte line, 1A-E2, specific for the HLA-A24-restricted epitope in Sin Nombre and Puumala virus G2 protein, and the human endothelial cell line, EA.hy926 that expresses HLA-A24 molecule. The cytotoxic T lymphocyte line recognized and lysed target cells infected with Sin Nombre virus, and in transwell permeability assays increased permeability of EA.hy926 cell monolayer infected with Sin Nombre virus or recombinant adenovirus expressing the Sin Nombre virus G2 protein. These results suggest that cytotoxic T lymphocyte activity contribute to capillary leakage observed in patients with hantavirus pulmonary syndrome or hemorrhagic fever with renal syndrome.
汉坦病毒感染可引发两种人类疾病，即肾综合征出血热和汉坦病毒肺综合征。这些疾病的典型特征分别是肾脏和肺部微血管床通透性增加。然而，毛细血管渗漏的机制尚不清楚。一些证据表明，汉坦病毒病的发病机制是由细胞毒性T淋巴细胞和靶器官中产生炎性细胞因子的其他免疫细胞介导的免疫反应。在本研究中，我们检测了病毒特异性细胞毒性T淋巴细胞在感染汉坦病毒的人内皮细胞通透性增加中的作用。我们使用了一种人CD8(+)汉坦病毒特异性细胞毒性T淋巴细胞系1A-E2，它对辛诺柏病毒和普马拉病毒G2蛋白中HLA-A24限制性表位具有特异性，以及表达HLA-A24分子的人内皮细胞系EA.hy926。该细胞毒性T淋巴细胞系识别并裂解感染辛诺柏病毒的靶细胞，在transwell通透性试验中，可增加感染辛诺柏病毒或表达辛诺柏病毒G2蛋白的重组腺病毒的EA.hy926细胞单层的通透性。这些结果表明，细胞毒性T淋巴细胞活性导致了汉坦病毒肺综合征或肾综合征出血热患者出现的毛细血管渗漏。
