CD8+ memory T cells
Memory T cells are unique cell population effectively protecting from second round of infection. The proportion of memory CD8+ T cells was significantly decreased with the increased severity, from mild, to moderate and severe COVID-19 patients [67]. The decrease of memory CD8+ T cells predisposed to be associated with severe COVID-19 among patients with elder age, male, and high body mass index (BMI) [67]. In contrast, other studies showed that the numbers of SARS-CoV-2-reactive memory CD8+ T cells were significantly increased in severe COVID-19 patients compared to patients with mild illness [67, 68]. As for CD8+ TEM, the percentage, the expression of CD8B and TRDC, and the acute inflammatory responses were significantly increased with COVID-19 disease severity [33]. The upregulation of BCL3 on CD8+TEM subset was essential for maximum IFN-γ secretion following secondary antigen stimulation in COVID-19 patients [34] (Figure 1). In addition, the naïve and CD8+TCM decreased while CD8+ terminal effector T cells (TTE, the subset of CD8+ TEM cells re-expressing CD45RA) increased in COVID-19 patients, which indicated a skew towards terminal differentiation [69]. The CD8+ TTEcells are mostly cytotoxic T cells expressing GZMA, GZMB, PRF1,and NKG7 (Figure 1). And CD8+TTE cells are enriched in individuals with severe infection [70] and recovered in the improved stage [71].
The proportion of CXCR6+ memory CD8+T cells was significantly higher among both mild and moderate COVID-19, while lower among severe COVID-19 than that among the normal group [67] (Figure 1). CXCR6+ memory CD8+ T cells were found to exhibit a notable polyfunctionality, including elevation of T cell activation, proliferation, migration, and chemotaxis. The enhanced interactions of CXCR6+ memory CD8+ T cells with epithelial cells facilitate the recruitment of this specific population of T cells to airways, promoting CD8+ T cell-mediated immunity against COVID-19 infection [67] Another cell population CD8+ TRM identified based on the expression of ZNF683 and ITGAE, was significantly increased in mild COVID-19 patients compared to critical COVID-19 patients [64]. In mild COVID-19, CD8+TRM cells had good effector functions and antigen-driven clonal expansion, while in critical COVID-19 patients they showed more naïve state and failed to undergo expansion [64] (Figure 1). Moreover, SARS-CoV-2-infected children showed a distinct CD8+ memory T cells that were almost absent in adults, while whether these cells help to protect the children against further reinfection is unclear [64]. Unlike CD4+ memory T cells, there was little evidence of cross-reactive CD8+ memory T cells against SARS-CoV-2 infection [43]. In addition, SARS-CoV-2 specific T cell immunity can be detected at least 8 months after infection [72], and consistently even longer (3 months to 6 years) for SARS-CoV specific memory T cells [73]. Therefore, further studies are necessary to understanding the mechanisms of generation and maintenance of long-term SARS-CoV-2-specific memory T cells to provide long-lasting antiviral protection.