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

• Published in: Viruses 2022-01, Vol.14 (1), p.130
• Main Authors: Cimini, Eleonora, Grassi, Germana, Beccacece, Alessia, Casetti, Rita, Castilletti, Concetta, Capobianchi, Maria Rosaria, Nicastri, Emanuele, Agrati, Chiara
• Format: Article
• Language: English
• Subjects: Adaptation, Physiological; Adult; Antimicrobial agents; CD38 antigen; Cell activation; Cell differentiation; Communication; COVID-19; Cytotoxicity; Dengue - immunology; Dengue fever; dengue infection; exhaustion marker; Flow Cytometry; Hepatitis A Virus Cellular Receptor 2 - genetics; Hepatitis A Virus Cellular Receptor 2 - metabolism; Histocompatibility antigen HLA; Humans; Immunity, Innate; Immunoregulation; Infections; Infectious diseases; innate immune response; Interferon-gamma - metabolism; Intraepithelial Lymphocytes - immunology; Leukocytes (mononuclear); Leukocytes, Mononuclear - immunology; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Male; Middle Aged; Pathogenesis; Patients; PD-1; PD-1 protein; Peripheral blood mononuclear cells; Phenotypes; Serology; Software; Statistical analysis; T-Lymphocyte Subsets - immunology; TIM-3; Viral infections; Viruses; Vδ2 T cells; γ-Interferon
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v14010130

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.