γδT cells
γδT cells are distinct subset of T cells composing TCRγ and TCRδ chains in parallel to αβT cells. Like NKT cells, γδT cells serve as a bridge between innate and adaptive immunity and have multiple functions, including recognizing and presenting antigens, helping B cells, secreting cytokines and so on [18]. Fluorescence-activated cell sorting (FACS) analysis demonstrated that γδ T cell proportion decreased accompanied with high levels of CD69 and PD-1 in COVID-19 patients [18, 78]. ScRNA-seq analysis further supported three times less γδ T cells in peripheral blood from COVID-19 patients than those from the healthy controls [79]. However, broncho-alveolar lavage fluids from COVID-19 patients encompassed more γδ T cells than controls [75, 79, 80]. γδT cells expressed transcriptional markers, such as CD2, CD5, CD7, CD8A , CD8B, TRDC, and TRGV9 [23] (Figure 1). In addition, the expression of CD3E was increased butCD3ζ (CD247 ) was suppressed on γδT cells, suggesting compromised T-cell signaling in COVID-19 patients [23]. Meanwhile, the response to IFN-α was significantly downregulated whereas responses to IL-12 was increased in severe patients [23, 33]. γδ T cells can secrete cytokines, including perforin, granzyme, IFN-γ, TNF-α, IL-6 and IL-17, demonstrating their antiviral capacity and pro-inflammatory activity [18]. Thus, the γδ T cell-based treatments have the possibility to cause serious cytokine storm, which need careful assessment.