PD-1-Expressing SARS-CoV-2-Specific CD8 + T Cells Are Not Exhausted, but Functional in Patients with COVID-19
Authors
Min-Seok Rha ; Hye Won Jeong ; Jae-Hoon Ko ; Seong Jin Choi ; In-Ho Seo ; Jeong Seok Lee ; Moa Sa ; A Reum Kim ; Eun-Jeong Joo ; Jin Young Ahn ; Jung Ho Kim ; Kyoung-Ho Song ; Eu Suk Kim ; Dong Hyun Oh ; Mi Young Ahn ; Hee Kyoung Choi ; Ji Hoon Jeon ; Jae-Phil Choi ; Hong Bin Kim ; Young Keun Kim ; Su-Hyung Park ; Won Suk Choi ; Jun Yong Choi ; Kyong Ran Peck ; Eui-Cheol Shin
CD8(+) T cell ; COVID-19 ; IFN-γ ; MHC class I multimer ; Memory T cell ; PD-1 ; SARS-CoV-2
Abstract
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.