In Acute Dengue Infection, High TIM-3 Expression May Contribute to the Impairment of IFNγ Production by Circulating Vδ2 T Cells

Viruses. 2022 Jan 12;14(1):130. doi: 10.3390/v14010130.

Abstract

γδ T cells are innate cells able to quickly eliminate pathogens or infected/tumoral cells by their antiviral and adjuvancy activities. The role of γδ T cells during Dengue Viral Infection (DENV) infection is not fully elucidated. Nevertheless, human primary γδ T cells have been shown to kill in vitro DENV-infected cells, thus highlighting their possible antiviral function. The aim of this work was to characterize the phenotype and function of Vδ2 T cells in DENV patients. Fifteen DENV patients were enrolled for this study and peripheral blood mononuclear cells (PBMC) were used to analyze Vδ2-T-cell frequency, differentiation profile, activation/exhaustion status, and functionality by multiparametric flow cytometry. Our data demonstrated that DENV infection was able to significantly reduce Vδ2-T-cell frequency and to increase their activation (CD38 and HLA-DR) and exhaustion markers (PD-1 and TIM-3). Furthermore, Vδ2 T cells showed a reduced capability to produce IFN-γ after phosphoantigenic stimulation that can be associated to TIM-3 expression. Several studies are needed to depict the possible clinical impact of γδ-T-cell impairment on disease severity and to define the antiviral and immunoregulatory activities of γδ T cells in the first phases of infection.

Keywords: PD-1; TIM-3; Vδ2 T cells; dengue infection; exhaustion marker; innate immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Adult
  • Dengue / immunology*
  • Flow Cytometry
  • Hepatitis A Virus Cellular Receptor 2 / genetics
  • Hepatitis A Virus Cellular Receptor 2 / metabolism*
  • Humans
  • Immunity, Innate
  • Interferon-gamma / metabolism*
  • Intraepithelial Lymphocytes / immunology*
  • Leukocytes, Mononuclear / immunology
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • T-Lymphocyte Subsets / immunology

Substances

  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • Interferon-gamma