Human Zika infection induces a reduction of IFN-γ producing CD4 T-cells and a parallel expansion of effector Vδ2 T-cells

Human Zika infection induces a reduction of IFN-γ producing CD4 T-cells and a parallel expansion of effector Vδ2 T-cells
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DOI:
10.1038/s41598-017-06536-x
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发表时间:
2017-07-24
期刊:
影响因子:
4.6
通讯作者:
Agrati, Chiara
Agrati, Chiara
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cimini, Eleonora;Castilletti, Concetta;Agrati, Chiara

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人类对寨卡病毒(ZIKV)感染的免疫反应的定义是一个关键问题,对于确定对疫苗研发和发病机制研究有用的保护特征至关重要。目前尚无关于人类寨卡病毒感染急性期细胞免疫反应的数据,其在保护和/或发病机制中的作用需要阐明。我们研究并比较了急性寨卡病毒和登革热病毒(DENV)感染患者的T细胞表型和功能。在寨卡病毒和登革热病毒感染期间均观察到T细胞的显著激活。寨卡病毒感染的特征是CD4 T细胞向效应细胞分化,以及产生干扰素 -γ的CD4 T细胞频率较低。此外,在寨卡病毒感染患者中特异性地观察到表达Vδ2 TCR的CD3 + CD4 - CD8 - T细胞亚群的大量扩增。Vδ2 T细胞呈现终末分化表型,表达颗粒酶B,并保持其产生干扰素 -γ的能力。这些发现为自限性感染期间的免疫反应特征提供了新的认识,可能有助于疫苗效力的确定以及识别严重感染可能的免疫 - 发病机制。
The definition of the immunological response to Zika (ZIKV) infection in humans represents a key issue to identify protective profile useful for vaccine development and for pathogenesis studies. No data are available on the cellular immune response in the acute phase of human ZIKV infection, and its role in the protection and/ or pathogenesis needs to be clarified. We studied and compared the phenotype and functionality of T-cells in patients with acute ZIKV and Dengue viral (DENV) infections. A significant activation of T-cells was observed during both ZIKV and DENV infections. ZIKV infection was characterized by a CD4 T cell differentiation toward effector cells and by a lower frequency of IFN-. producing CD4 T cells. Moreover, a substantial expansion of CD3+ CD4-CD8-T-cell subset expressing Vd2 TCR was specifically observed in ZIKV patients. Vd2 T cells presented a terminally differentiated profile, expressed granzyme B and maintained their ability to produce IFN-gamma. These findings provide new knowledge on the immune response profile during self-limited infection that may help in vaccine efficacy definition, and in identifying possible immuno-pathogenetic mechanisms of severe infection.