Making a case for using γδ T cells against SARS-CoV-2.

Intensive worldwide efforts are underway to determine both the pathogenesis of SARS-CoV-2 infection and the immune responses in COVID-19 patients in order to develop effective therapeutics and vaccines. One type of cell that may contribute to these immune responses is the γδ T lymphocyte, which plays a key role in immunosurveillance of the mucosal and epithelial barriers by rapidly responding to pathogens. Although found in low numbers in blood, γδ T cells consist the majority of tissue-resident T cells and participate in the front line of the host immune defense. Previous studies have demonstrated the critical protective role of γδ T cells in immune responses to other respiratory viruses, including SARS-CoV-1. However, no studies have profoundly investigated these cells in COVID-19 patients to date. γδ T cells can be safely expanded in vivo using existing inexpensive FDA-approved drugs such as bisphosphonate, in order to test its protective immune response to SARS-CoV-2. To support this line of research, we review insights gained from previous coronavirus research, along with recent findings, discussing the potential role of γδ T cells in controlling SARS-CoV-2. We conclude by proposing several strategies to enhance γδ T cell's antiviral function, which may be used in developing therapies for COVID-19.

The Role of Gamma-Delta T Cells in Diseases of the Central Nervous System.

Gamma-delta (γδ) T cells are a subset of T cells that promote the inflammatory responses of lymphoid and myeloid lineages, and are especially vital to the initial inflammatory and immune responses. Given the capability to connect crux inflammations of adaptive and innate immunity, γδ T cells are responsive to multiple molecular cues and can acquire the capacity to induce various cytokines, such as GM-CSF, IL-4, IL-17, IL-21, IL-22, and IFN-γ. Nevertheless, the exact mechanisms responsible for γδ T cell proinflammatory functions remain poorly understood, particularly in the context of the central nervous system (CNS) diseases. CNS disease, usually leading to irreversible cognitive and physical disability, is becoming a worldwide public health problem. Here, we offer a review of the neuro-inflammatory and immune functions of γδ T cells, intending to understand their roles in CNS diseases, which may be crucial for the development of novel clinical applications.

Commensal Microbiome Expands Tγδ17 Cells in the Lung and Promotes Particulate Matter-Induced Acute Neutrophilia.

Particulate matter (PM) induces neutrophilic inflammation and deteriorates the prognosis of diseases such as cardiovascular diseases, cancers, and infections, including COVID-19. Here, we addressed the role of γδ T cells and intestinal microbiome in PM-induced acute neutrophilia. γδ T cells are a heterogeneous population composed of Tγδ1, Tγδ2, Tγδ17, and naïve γδ T cells (TγδN) and commensal bacteria promote local expansion of Tγδ17 cells, particularly in the lung and gut without affecting their Vγ repertoire. Tγδ17 cells are more tissue resident than Tγδ1 cells, while TγδN cells are circulating cells. IL-1R expression in Tγδ17 cells is highest in the lung and they outnumber all the other type 17 cells such as Th17, ILC3, NKT17, and MAIT17 cells. Upon PM exposure, IL-1ß-secreting neutrophils and IL-17-producing Tγδ17 cells attract each other around the airways. Accordingly, PM-induced neutrophilia was significantly relieved in γδ T- or IL-17-deficient and germ-free mice. Collectively, these findings show that the commensal microbiome promotes PM-induced neutrophilia in the lung via Tγδ17 cells.