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-γ (IFN-γ)-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-γ-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.