CD4+ T Cells
CD4+ T cells are key players in the immune response to viral infections as they help promote antibody production from B cells as well as generate cytotoxic and memory CD8+ T cells. Naïve CD4+ T cells differentiate into different T cell subsets following activation. The immune response to SARS-CoV-2 involves the activation of CD4+ T cells, as seen by the expression of activation-related markers, such as CD40 Ligand/TNFSF5, CD69, CD38, 4-1BB/TNFRSF9/CD137, PD-1, and HLA-DR, on SARS-CoV-2-reactive cells; however, the specific CD4+ T cells that respond to SARS-CoV-2 and their role in the immune response is still not clearly understood. Research has reported the activation of T helper (Th)1, Th2, Th17, regulatory (Treg), and cytotoxic Th (CD4-CTLs) cells following SARS-CoV-2 infection. Follicular helper T (Tfh) cells have also been shown to be activated. Tfh cells localize to B cell follicles and help mediate the survival and differentiation of B cells into antibody-producing plasma cells and memory B cells. A small proportion of Tfh cells can also circulate in the blood where they promote antibody secretion and immunoglobulin class-switching. These circulating Tfh (cTfh) cells have also been shown to be present at higher frequencies in convalescent COVID-19 individuals. Despite these reports, the landscape of the cellular immunity remains unclear as further studies have described the reduction of T cell numbers (i.e., lymphopenia) and function (i.e., T cell exhaustion) in severe cases of COVID-19.
View the cell markers for CD4+ Th cells with our Interactive Cell Marker Tool.
CD8+ Cytotoxic T Cells
CD8+ cytotoxic T (CD8-CTL) cells are a key player in the immune response to SARS-CoV-2 infection. CD8-CTL cells eliminate virus-infected cells by triggering apoptosis, either through the secretion of cytolytic granules or the activation of the TNF superfamily of death receptors. Research has shown a heterogeneity of CD8-CTL responses following SARS-CoV-2 infection. A strong CD8-CTL response has been reported in individuals with mild COVID-19; however, patients severely ill with COVID-19 appear to suffer from lymphopenia, which affects many immune cell types, including CD8-CTL cells.
|Naïve CD8+ T Cells
||CD3+ CD8+ CD45RA+ CD45RO- CCR7+
|Central Memory CD8+ T Cells
||CD3+ CD8+ CD45RA- CD45RO+ CCR7+
|Effector Memory CD8+ T Cells
||CD3+ CD8+ CD45RA- CD45RO+ CCR7-
|CD8+ Cytotoxic T Cells
||CD3+ CD8+ TCR α/β+
B cells are an integral part of the humoral immune response to viral infections due to their ability to produce antibodies. Immunocompetent naïve mature B cells are activated by binding of the foreign antigen to the mature B cell receptor, in the presence of a co-stimulatory signal. The activated B cells participate in germinal center reactions where they differentiate into memory B cells or long-lived, antibody-secreting plasma cells. SARS-CoV-2 infection induces the production of IgM antibodies, followed by IgG antibodies. Studies have shown that antibody levels significantly fall 2-3 months after infection; however, additional research has shown a robust memory B cell response in convalescent COVID-19 patients.
View the cell markers for B cells with our Interactive Cell Marker Tool.
Natural Killer (NK) Cells
NK cells are part of the innate immune system. They serve as the first line of defense against viral infections. NK cells attack and eliminate virus-infected cells by secreting proinflammatory cytokines and triggering Perforin/Granzyme-induced cell lysis. NK cells have also been shown to regulate adaptive immune responses. Multiple studies have shown that NK cell levels and cytolytic activity function are reduced in individuals with severe COVID-19. This diminished NK function is thought to underlie the elevated inflammatory response seen in severe COVID-19 cases, perhaps due to the reduced clearance of infected cells or the unchecked response of adaptive immune cells.
View the cell markers for NK cells with our Interactive Cell Marker Tool.
Macrophages are cells of the innate immune system that are responsible for a multitude of immune functions including immune surveillance, antigen presentation, and phagocytosis of debris, dead cells, and pathogens. Tissue-resident macrophages are a heterogeneous group of cells that perform tissue-specific immune and homeostatic functions. Alveolar macrophages, which reside in the lungs, are critical for recovery from viral infections as they phagocytize neutralized viruses and apoptotic cells, clearing the debris from the lungs.
View the steady-state and activation cell markers for macrophages with our Interactive Cell Marker Tool.