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具有寨卡病毒感染史的母亲及其子女队列中记忆性 CD4 和 CD8 T 细胞的差异寿命。

Differential Longevity of Memory CD4 and CD8 T Cells in a Cohort of the Mothers With a History of ZIKV Infection and Their Children.

机构信息

Laboratory of Viral Immunology, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.

Multiuser Laboratory for Research in Nephrology and Medical Science, School of Medicine, Universidade Federal Fluminense, Niterói, Brazil.

出版信息

Front Immunol. 2021 Feb 12;12:610456. doi: 10.3389/fimmu.2021.610456. eCollection 2021.

Abstract

Zika virus (ZIKV) infection causes for mild and self-limiting disease in healthy adults. In newborns, it can occasionally lead to a spectrum of malformations, the congenital Zika syndrome (CZS). Thus, little is known if mothers and babies with a history of ZIKV infection were able to develop long-lasting T-cell immunity. To these issues, we measure the prevalence of ZIKV T-cell immunity in a cohort of mothers infected to the ZIKV during pregnancy in the 2016-2017 Zika outbreak, who gave birth to infants affected by neurological complications or asymptomatic ones. Twenty-one mothers and 18 children were tested for IFN-γ ELISpot and T-cell responses for flow cytometry assays in response to CD4 ZIKV and CD8 ZIKV megapools (CD4 ZIKV MP and CD8 ZIKV MP). IFN-γ ELISpot responses to ZIKV MPs showed an increased CD4 and CD8 T-cell responses in mothers compared to children. The degranulation activity and IFN-γ-producing CD4 T cells were detected in most mothers, and children, while in CD8 T-cells, low responses were detected in these study groups. The total Temra T cell subset is enriched for IFN-γ+ CD4 T cells after stimulation of CD4 ZIKV MP. Donors with a history of ZIKV infection demonstrated long-term CD4 T cell immunity to ZIKV CD4 MP. However, the same was not observed in CD8 T cells with the ZIKV CD8 MP. One possibility is that the cytotoxic and pro-inflammatory activities of CD8 T cells are markedly demonstrated in the early stages of infection, but less detected in the disease resolution phase, when the virus has already been eliminated. The responses of mothers' T cells to ZIKV MPs do not appear to be related to their children's clinical outcome. There was also no marked difference in the T cell responses to ZIKV MP between children affected or not with CZS. These data still need to be investigated, including the evaluation of the response of CD8 T cells to other ZIKV peptides.

摘要

寨卡病毒(ZIKV)感染在健康成年人中引起轻度自限性疾病。在新生儿中,它偶尔会导致一系列畸形,即先天性寨卡综合征(CZS)。因此,对于有 ZIKV 感染史的母亲和婴儿是否能够产生持久的 T 细胞免疫,人们知之甚少。针对这些问题,我们在 2016-2017 年寨卡病毒爆发期间感染了 ZIKV 的孕妇队列中测量了 ZIKV T 细胞免疫的流行率,这些孕妇所生的婴儿患有神经并发症或无症状。21 名母亲和 18 名儿童接受了 IFN-γ ELISpot 和 T 细胞反应流式细胞术检测,以响应 CD4 ZIKV 和 CD8 ZIKV 巨池(CD4 ZIKV MP 和 CD8 ZIKV MP)。与儿童相比,母亲的 ZIKV MPs 的 IFN-γ ELISpot 反应显示出增加的 CD4 和 CD8 T 细胞反应。在大多数母亲和儿童中检测到脱颗粒活性和 IFN-γ 产生的 CD4 T 细胞,而在 CD8 T 细胞中,这些研究组的反应较低。在刺激 CD4 ZIKV MP 后,Temra T 细胞亚群中总 CD4+T 细胞丰富。有 ZIKV 感染史的供体对 ZIKV CD4 MP 表现出长期的 CD4 T 细胞免疫。然而,在 ZIKV CD8 MP 中,同样的情况并未观察到。一种可能性是,在感染的早期阶段,CD8 T 细胞的细胞毒性和促炎活性明显,但在疾病消退阶段,当病毒已被消除时,检测到的活性较少。母亲的 T 细胞对 ZIKV MPs 的反应似乎与她们孩子的临床结果无关。在患有或不患有 CZS 的儿童中,对 ZIKV MP 的 T 细胞反应也没有明显差异。这些数据仍需进一步研究,包括评估 CD8 T 细胞对其他 ZIKV 肽的反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b284/7928292/b35756b07c73/fimmu-12-610456-g0001.jpg

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