Phenotypes and functions of SARS-CoV-2-specific CD8+ T cells in patients with acute COVID-19. During acute COVID-19, SARS-CoV-2-specific CD8⁺ T cells express not only activation markers (CD38 and HLA-DR), a proliferation marker (Ki-67), and cytotoxic molecules (perforin and granzyme B), but also immune checkpoint inhibitory receptors (PD-1 and TIM-3). However, SARS-CoV-2-specific CD8⁺ T cells produce IFN-γ regardless of PD-1 expression, indicating that SARS-CoV-2-specific PD-1⁺CD8⁺ T cells are functional, not exhausted.|@|~(^,^)~|@|Differentiation of SARS-CoV-2-specific CD8+ T cells during the convalescent period of COVID-19. From the early convalescent to the late convalescent phases, the frequency of SARS-CoV-2-specific CD8⁺ T cells expressing CD38 and PD-1 decreases gradually, whereas the frequency of SARS-CoV-2-specific CD8⁺ T cells expressing CCR7, CD45RA, and CD127 increases. In particular, among SARS-CoV-2-specific CD8⁺ T cells, the frequency of CCR7⁺CD45RA⁺CD95⁺ stem cell-like memory T (TSCM) cells that have the capacity for self-renewal and multipotency increases in the late convalescent phase. The generation of TSCM cells is also observed among SARS-CoV-2-specific CD4⁺ T cells.

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