PD-1-Expressing SARS-CoV-2-Specific CD8+ T Cells Are Not Exhausted, but Functional in Patients with COVID-19

Memory T cell responses have been demonstrated in COVID-19 convalescents, but ex vivo phenotypes of SARS-CoV-2-specific T cells have been unclear. We detected SARS-CoV-2-specific CD8(+) T cells by MHC class I multimer staining and examined their phenotypes and functions in acute and convalescent COVID-19. Multimer(+) cells exhibited early differentiated effector-memory phenotypes in the early convalescent phase. The frequency of stem-like memory cells was increased among multimer cells in the late convalescent phase. Cytokine secretion assays combined with MHC class I multimer staining revealed that the proportion of interferon-gamma (IFN-gamma)-producing cells was significantly lower among SARS-CoV-2-specific CD8(+) T cells than those specific to influenza A virus. Importantly, the proportion of IFN-gamma-producing cells was higher in PD-1(+) cells than PD-1(-) cells among multimer cells, indicating that PD-1-expressing, SARS-CoV-2-specific CD8(+) T cells are not exhausted, but functional. Our current findings provide information for understanding of SARS-CoV-2-specific CD8(+) T cells elicited by infection or vaccination.

Automated summary

Memory T cell responses have been observed in COVID-19 convalescents, with specific T cells showing different phenotypes during the recovery phase. SARS-CoV-2-specific CD8(+) T cells displayed early differentiated effector-memory phenotypes in the early convalescent phase and an increased proportion of stem-like memory cells in the late convalescent phase. Compared to influenza A virus-specific CD8(+) T cells, SARS-CoV-2-specific CD8(+) T cells had a lower frequency of IFN-gamma-producing cells. Additionally, PD-1-expressing SARS-CoV-2-specific CD8(+) T cells were functional rather than exhausted.