γδ T Cells in Emerging Viral Infection: An Overview

Abstract

New emerging viruses belonging to the Coronaviridae, Flaviviridae, and Filoviridae families are serious threats to public health and represent a global concern. The surveillance to monitor the emergence of new viruses and their transmission is an important target for public health authorities. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an excellent example of a pathogen able to cause a pandemic. In a few months, SARS-CoV-2 has spread globally from China, and it has become a world health problem. Gammadelta (γδ) T cell are sentinels of innate immunity and are able to protect the host from viral infections. They enrich many tissues, such as the skin, intestines, and lungs where they can sense and fight the microbes, thus contributing to the protective immune response. γδ T cells perform their direct antiviral activity by cytolytic and non-cytolytic mechanisms against a wide range of viruses, and they are able to orchestrate the cellular interplay between innate and acquired immunity. For their pleiotropic features, γδ T cells have been proposed as a target for immunotherapies in both cancer and viral infections. In this review, we analyzed the role of γδ T cells in emerging viral infections to define the profile of the response and to better depict their role in the host protection.

T cells in health and disease

“…974,975 Moreover, γδ T cells exhibit a potent antiviral activity against a variety of viruses. 976 Upon recognition of viral antigens, γδ T cells become activated and express increased proinflammatory cytokines (IFN-γ and TNF-α) and cytotoxic molecules (perforin and granzymes) for pathogen clearance. 976 During SARS-CoV2 infection, the frequency of γδ T cells is reduced in the circulation but increased in the airway tissues.…”

“…976 Upon recognition of viral antigens, γδ T cells become activated and express increased proinflammatory cytokines (IFN-γ and TNF-α) and cytotoxic molecules (perforin and granzymes) for pathogen clearance. 976 During SARS-CoV2 infection, the frequency of γδ T cells is reduced in the circulation but increased in the airway tissues. 976 Both circulating and tissue-colonized γδ T cells have upregulated activation phenotypes (CD25, CD69, PD-1, IFN-γ and IL-18), suggesting an antiviral activity.…”

The intestinal γδ T cells: functions in the gut and in the distant organs

“…gd T cells are now a hot topic, and several impressive articles review the key functional roles of the gd T cells in transplantation (24), anti-viral infection (25), and responses to the gut microbiota (26), as well as the gd TCR in diagnosis and prognosis of Mouse intestinal gd T cells. The intestinal epithelium is composed of a single layer of cells that separate microbes in the lumen from the lamina propria.…”

Serum vitamin D deficiency is associated with increased risk of γδ T cell exhaustion in HBV‐infected patients

“…Mechanistically, γδ T cells mediate cytokine production that can inhibit viral replication and enhance the activity of other immune cells such as dendritic cells, natural killer (NK) cells and CD8 + T cells [20][21][22]. Vδ2 T cells can produce IFN-γ, which has antiviral activity against a broad range of viruses, including HBV, HCV, influenza virus and human immunodeficiency virus (HIV) [14,[23][24][25]. Therefore, strategies such as adoptive transfer of ex vivo-expanded γδ T cells and modulation of their function are highly promising for the treatment of HBV infection.…”

“…Although γδ T cells have been shown to have both direct and indirect antiviral effects against HBV [15,23]. However, HBV has adopted several strategies to evade immune surveillance and persist in the host [26,27].…”