Cutting Edge: Transcriptional Profiling Reveals Multifunctional and Cytotoxic Antiviral Responses of Zika Virus-Specific CD8+ T Cells

J Immunol. 2018 Dec 15;201(12):3487-3491. doi: 10.4049/jimmunol.1801090. Epub 2018 Nov 9.

Abstract

Zika virus (ZIKV) constitutes an increasing public health problem. Previous studies have shown that CD8+ T cells play an important role in ZIKV-specific protective immunity. We have previously defined antigenic targets of the ZIKV-specific CD8+ T cell response in humans. In this study, we characterized the quality and phenotypes of these responses by a combined use of flow cytometry and transcriptomic methods, using PBMCs from donors deriving from different geographical locations collected in the convalescent phase of infection. We show that ZIKV-specific CD8+ T cells are characterized by a polyfunctional IFN-γ signature with upregulation of TNF-α, TNF receptors, and related activation markers, such as CD69, as well as a cytotoxic signature characterized by strong upregulation of GZMB and CRTAM. The signature is stable and not influenced by previous dengue virus exposure, geographical location, or time of sample collection postinfection. To our knowledge, this work elucidates the first in-depth characterization of human CD8+ T cells responding to ZIKV infection.

Publication types

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

MeSH terms

  • Antigens, Viral / immunology
  • CD8-Positive T-Lymphocytes / physiology*
  • Cells, Cultured
  • Cytotoxicity, Immunologic
  • Epitopes, T-Lymphocyte / immunology
  • Gene Expression Profiling
  • Granzymes / genetics
  • Humans
  • Immunoglobulins / genetics
  • Immunophenotyping
  • Interferon-gamma / genetics
  • Receptors, Tumor Necrosis Factor / genetics
  • Tumor Necrosis Factor-alpha / genetics
  • Zika Virus / physiology*
  • Zika Virus Infection / immunology*

Substances

  • Antigens, Viral
  • Epitopes, T-Lymphocyte
  • Immunoglobulins
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • class-I restricted T cell-associated molecule
  • Interferon-gamma
  • GZMB protein, human
  • Granzymes