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

Jessica Badolato-Corrêa,Helver Gonçalves Dias,Claudete Aparecida Araújo Cardoso,Daniela Weiskopf,Alessandro Sette,Mariana Gandini,Alex Pauvolid-Corrêa,Débora Familiar-Macedo,Renata Artimos De Oliveira Vianna,Luzia Maria De-Oliveira-Pinto,Monique Da Rocha Queiroz Lima,Alba Grifoni,Elzinandes Leal De Azeredo,Iury Amancio Paiva,Fabiana Rabe Carvalho,Solange Artimos De Oliveira,Caroline Fernandes-Santos,Andréa Alice Silva,Silvia Maria Baeta Cavalcanti

doi:10.3389/fimmu.2021.610456

Abstract

Background: 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.Results: 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.Conclusion: 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.

Highlights

The emergence of Zika virus (ZIKV) in dengue-endemic regions creates a potentially alarming scenario, as those caused by the ZIKV epidemic spread across countries, especially the Americas, during 2015–2016 [1, 2]
We studied ZIKV memory T cell responses from a cohort of mothers infected with ZIKV during pregnancy in the 2016–2017 Zika outbreak who gave birth to infants affected by neurological complications or asymptomatic ones
One mother who had a child with congenital Zika syndrome (CZS) (1 out of 21; 4.8%) had anti-dengue virus (DENV) immunoglobulin G (IgG) but not anti-ZIKV IgG

Summary

Introduction

The emergence of ZIKV in dengue-endemic regions creates a potentially alarming scenario, as those caused by the ZIKV epidemic spread across countries, especially the Americas, during 2015–2016 [1, 2]. DENV and ZIKV are members of the family Flaviviridae and are among the several medically important viruses [5] Both are spread via the bite of infected mosquitoes, Aedes spp., whose ecological niches expand beyond the tropical and subtropical regions [6]. 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

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