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

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

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.

Keywords: T cells; Zika; congenital Zika syndrome (CZS); memory; pregnancy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cross Reactions / immunology
  • Cross-Sectional Studies
  • Female
  • Humans
  • Immunity, Maternally-Acquired
  • Immunologic Memory*
  • Immunophenotyping
  • Neutralization Tests
  • Pregnancy
  • Pregnancy Complications, Infectious
  • Young Adult
  • Zika Virus / immunology*
  • Zika Virus Infection / blood
  • Zika Virus Infection / epidemiology
  • Zika Virus Infection / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral