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

gamma delta T cells are innate cells able to quickly eliminate pathogens or infected/tumoral cells by their antiviral and adjuvancy activities. The role of gamma delta T cells during Dengue Viral Infection (DENV) infection is not fully elucidated. Nevertheless, human primary gamma delta 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 V delta 2 T cells in DENV patients. Fifteen DENV patients were enrolled for this study and peripheral blood mononuclear cells (PBMC) were used to analyze V delta 2-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 V delta 2-T-cell frequency and to increase their activation (CD38 and HLA-DR) and exhaustion markers (PD-1 and TIM-3). Furthermore, V delta 2 T cells showed a reduced capability to produce IFN-gamma after phosphoantigenic stimulation that can be associated to TIM-3 expression. Several studies are needed to depict the possible clinical impact of gamma delta-T-cell impairment on disease severity and to define the antiviral and immunoregulatory activities of gamma delta T cells in the first phases of infection.

Automated summary

Gamma delta T cells play a role in eliminating pathogens and infected/tumoral cells. Their role in Dengue Viral Infection (DENV) is not fully understood. This study characterized V delta 2 T cells in DENV patients and found that DENV infection reduced their frequency and increased activation and exhaustion markers. The functionality of V delta 2 T cells, especially IFN-gamma production, was also affected. Further studies are needed to understand the clinical impact of gamma delta T cell impairment in disease severity and their antiviral and immunoregulatory activities.