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首页> 外文期刊>EBioMedicine >The Role of Heterotypic DENV-specific CD8^+T Lymphocytes in an Immunocompetent Mouse Model of Secondary Dengue Virus Infection
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The Role of Heterotypic DENV-specific CD8^+T Lymphocytes in an Immunocompetent Mouse Model of Secondary Dengue Virus Infection

机译：异型DENV特异性CD8 ^ + T淋巴细胞在继发登革热病毒感染的免疫小鼠模型中的作用

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摘要

Dengue is the most prevalent arthropod-borne viral disease worldwide and is caused by the four dengue virus serotypes (DENV-1-4). Sequential heterologous DENV infections can be associated with severe disease manifestations. Here, we present an immunocompetent mouse model of secondary DENV infection using non mouse-adapted DENV strains to investigate the pathogenesis of severe dengue disease. C57BL/6 mice infected sequentially with DENV-1 (strain Puerto Rico/94) and DENV-2 (strain Tonga/74) developed low platelet counts, internal hemorrhages, and increase of liver enzymes. Cross-reactive CD8^+ T lymphocytes were found to be necessary and sufficient for signs of severe disease by adoptively transferring of DENV-1-immune CD8^+T lymphocytes before DENV-2 challenge. Disease signs were associated with production of tumor necrosis factor (TNF)-@a and elevated cytotoxicity displayed by heterotypic anti-DENV-1 CD8^+ T lymphocytes. These findings highlight the critical role of heterotypic anti-DENV CD8^+ T lymphocytes in manifestations of severe dengue disease.
机译：登革热是全球最普遍的节肢动物传播的病毒性疾病，由四种登革热病毒血清型（DENV-1-4）引起。顺序性异源DENV感染可能与严重的疾病表现有关。在这里，我们介绍了使用非小鼠适应性登革热病毒株的继发性登革热病毒感染的免疫小鼠模型，以研究严重登革热疾病的发病机理。依次感染DENV-1（波多黎各/ 94株）和DENV-2（汤加/ 74株）的C57BL / 6小鼠血小板计数低，内出血和肝酶增加。通过在DENV-2攻击之前过继转移DENV-1免疫的CD8 ^ + T淋巴细胞，发现交叉反应的CD8 ^ + T淋巴细胞对于严重疾病的征兆是必要的和充分的。疾病迹象与肿瘤坏死因子（TNF）-α的产生和异型抗DENV-1 CD8 ^ + T淋巴细胞显示出的细胞毒性升高有关。这些发现突出了异型抗DENV CD8 ^ + T淋巴细胞在严重登革热疾病表现中的关键作用。

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