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PLoS Pathog. 2019 Jan 24;15(1):e1007474. doi: 10.1371/journal.ppat.1007474. eCollection 2019 Jan.

CD4+ T cells promote humoral immunity and viral control during Zika virus infection.

Author information

1
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, United States of America.
2
Institute of Arboviruses, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
3
School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, Nakhon Ratchasima, Thailand.
4
Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, United States of America.

Abstract

Several Zika virus (ZIKV) vaccines designed to elicit protective antibody (Ab) responses are currently under rapid development, but the underlying mechanisms that control the magnitude and quality of the Ab response remain unclear. Here, we investigated the CD4+ T cell response to primary intravenous and intravaginal infection with ZIKV. Using the LysMCre+Ifnar1fl/fl (myeloid type I IFN receptor-deficient) C57BL/6 mouse models, we identified six I-Ab-restricted ZIKV epitopes that stimulated CD4+ T cells with a predominantly cytotoxic Th1 phenotype in mice primed with ZIKV. Intravenous and intravaginal infection with ZIKV effectively induced follicular helper and regulatory CD4+ T cells. Treatment of mice with a CD4+ T cell-depleting Ab reduced the plasma cell, germinal center B cell, and IgG responses to ZIKV without affecting the CD8+ T cell response. CD4+ T cells were required to protect mice from a lethal dose of ZIKV after infection intravaginally, but not intravenously. However, adoptive transfer and peptide immunization experiments showed a role for memory CD4+ T cells in ZIKV clearance in mice challenged intravenously. These results demonstrate that CD4+ T cells are required mainly for the generation of a ZIKV-specific humoral response but not for an efficient CD8+ T cell response. Thus, CD4+ T cells could be important mediators of protection against ZIKV, depending on the infection or vaccination context.

PMID:
30677097
PMCID:
PMC6345435
DOI:
10.1371/journal.ppat.1007474
[Indexed for MEDLINE]
Free PMC Article

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