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

表达PD-1的SARS-CoV-2特异性CD8+ T细胞在COVID-19患者体内并未耗竭,而是具有功能活性。

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作者: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

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.

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