CD8+ effector T cells
CD8+ effector T cells are the key population for
defending against viral infection through eliminating virus and
virus-infected cells. The proportion of CD8+ effector
T cells was higher in COVID-19 patients compared to the healthy group,
but lower in severe compared with non-severe group [23]. However,
another study performed by scRNA-seq analysis revealed that the number
of CD8+ effector T cells were increased in severe and
critical COVID-19 patients compared to healthy donors, which might be
associated with the low expression of ZBTB7B and high expression
of CBFB, EP300 and RUNX3 [24]. Meanwhile, the
dysfunction of CD8+ effector cells in severe and
critical COVID-19 patients manifested themselves in the high expression
of apoptosis-related genes (MAF ) and exhaustion-related genes,
and the attenuated function of proliferation [24]. The genes
enriched in “IL-17 signaling pathway” and “response to toxic
substance” expressed in the CD8+ effector T cells of
COVID-19 patients were down-regulated [24]. In contrast, activated
CD8+ T cells exhibited higher levels of cytotoxicity
molecules, such as GZMB and perforin in severe COVID-19 patients than in
the mild COVID-19 patients [62] (Figure 1). In addition, the
abundance of effector CD8+ T cells were diversity
across age groups. Older patients tend to have a high proportion of
effector CD8+T cells relative to younger counterparts
[42].
Similar to CD4+ effector T cells,
CD8+ effector-GZMK and CD8+effector-GNLY T cells were also found in COVID-19 patients.
CD8+ effector-GZMK cells uniquely expressingGZMK , showed highly exhausted status and high proportion of
clonal cells, whereas CD8+ effector-GNLY cells
expressing high level of GZMB/H and GNLY , showed high
proportion of activate state and clonal expansion, and enhanced
cytotoxicity [28, 33] (Figure 1). In bronchoalveolar lavage samples,
highly clonally expanded CD8+ T cells expressed higher
levels of GZMK, GZMA and FASLG and the tissue-residence
markers ITGA1, CXCR6 and JAML . This population had
upregulation of genes involved in activation, migration and
cytokine-related pathways in moderate cases and cell homeostasis,
translation initiation and nucleoside metabolic pathways in severe cases
[60]. In child patients, there were greater IFN, inflammasome
signaling, widespread T cell activation [63] and a subpopulation of
KLRC1 (NKG2A+) cytotoxic T cells (CTL2) predominantly
[64]. NKG2A is a lectin-like inhibitory receptor on cytotoxic T
cells and plays a role in limiting excessive activation, preventing
apoptosis and sustaining the virus-specific CD8+ T
cell response [64] (Figure 1). However, persisting stimulation of
CD8+ T-cells resulted in exhaustion. Therefore,
simultaneous consideration of improving virus-specific
CD8+ T cells activation, proliferation, cytotoxic
capacity and limiting exhaustion is needed for COVID-19 immunotherapy.