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

Rha, Min‐Seok; Jeong, Hye Won; Ko, J.H.; Choi, Seong Jin; Seo, In-Ho; Lee, Jeong Seok; Sa, Moa; Kim, A. Reum; Joo, Eun Jeong; Ahn, Jin Young; Kim, Jung Ho; Song, Kyoung Ho; Kim, Eu Suk; Oh, Dong Hyun; Ahn, Mi Young; Choi, Hee Kyoung; Jeon, Ju Hyun; Choi, Jaewon; Kim, Hong Bin; Kim, Young Keun; Park, Su–Hyung; Choi, Won Suk; Choi, Jun Yong; Peck, Kyong Ran; Shin, Eui Cheol

doi:10.1016/j.immuni.2020.12.002

Cited by 202 publications

(227 citation statements)

References 27 publications

(40 reference statements)

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“…To our knowledge, these are the first data to show, through direct comparison, that SARS-CoV-2-specific cellular immune responses are more efficient in asymptomatic than symptomatic individuals. Previous results that support our findings: a low IFN-γ production of total (De Biasi et al, 2020) and SARS-CoV-2-specific (Rha et al, 2021) T cells has been reported in COVID-19 patients, while conversely, a high quantity of IFN-γ RNA was found in CD4 T cells of asymptomatic individuals (Zhao et al, 2020 Preprint).…”

Section: Discussionsupporting

confidence: 91%

Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection

Bert

Clapham

Tan

et al. 2021

Journal of Experimental Medicine

295

208

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The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between antiviral and inflammatory features. SARS-CoV-2–specific T cells in individuals who clear SARS-CoV-2 without symptoms could reveal nonpathological yet protective characteristics. We longitudinally studied SARS-CoV-2–specific T cells in a cohort of asymptomatic (n = 85) and symptomatic (n = 75) COVID-19 patients after seroconversion. We quantified T cells reactive to structural proteins (M, NP, and Spike) using ELISpot and cytokine secretion in whole blood. Frequencies of SARS-CoV-2–specific T cells were similar between asymptomatic and symptomatic individuals, but the former showed an increased IFN-γ and IL-2 production. This was associated with a proportional secretion of IL-10 and proinflammatory cytokines (IL-6, TNF-α, and IL-1β) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2–specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2–infected individuals are not characterized by weak antiviral immunity; on the contrary, they mount a highly functional virus-specific cellular immune response.

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Section: Discussionsupporting

confidence: 91%

Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection

Bert

Clapham

Tan

et al. 2021

Journal of Experimental Medicine

295

208

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“…Several studies using overlapping peptide pools spanning different region of SARS-CoV-2 viral proteins have shown a broad range of T cell activation in convalescent COVID-19 patients (8,9,11,14,15,(31)(32)(33)(34)(35). Our work now provides a detailed characterization of minimal epitopes derived from the complete SARS-CoV-2 genome for their CD8 + T cell immunogenicity, immunodominance, and functional and phenotypical characteristics in COVID-19 patients and healthy donors.…”

Section: Discussionmentioning

confidence: 77%

SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8 ⁺ T cell activation in COVID-19 patients

et al. 2021

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T cells are important for effective viral clearance, elimination of virus-infected cells and long-term disease protection. To examine the full-spectrum of CD8+ T cell immunity in COVID-19, we experimentally evaluated 3141 major histocompatibility (MHC) class I-binding peptides covering the complete SARS-CoV-2 genome. Using DNA-barcoded peptide-MHC complex (pMHC) multimers combined with a T cell phenotype panel, we report a comprehensive list of 122 immunogenic and a subset of immunodominant SARS-CoV-2 T cell epitopes. Substantial CD8+ T cell recognition was observed in COVID-19 patients, with up to 27% of all CD8+ lymphocytes interacting with SARS-CoV-2-derived epitopes. Most immunogenic regions were derived from open reading frame (ORF) 1 and ORF3, with ORF1 containing most of the immunodominant epitopes. CD8+ T cell recognition of lower affinity was also observed in healthy donors toward SARS-CoV-2-derived epitopes. This pre-existing T cell recognition signature was partially overlapping with the epitope landscape observed in COVID-19 patients and may drive the further expansion of T cell responses to SARS-CoV-2 infection. Importantly the phenotype of the SARS-CoV-2-specific CD8+ T cells, revealed a strong T cell activation in COVID-19 patients, while minimal T cell activation was seen in healthy individuals. We found that patients with severe disease displayed significantly larger SARS-CoV-2-specific T cell populations compared to patients with mild diseases and these T cells displayed a robust activation profile. These results further our understanding of T cell immunity to SARS-CoV-2 infection and hypothesize that strong antigen-specific T cell responses are associated with different disease outcomes.

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“…However, our group recently examined SARS-CoV-2-specific CD8 + T cells using MHC-I multimers and demonstrated that IFN-γ is produced by SARS-CoV-2-specific CD8 + T cells in acute and convalescent COVID-19 patients regardless of PD-1 expression (Rha et al, 2021) (Fig. 1).…”

Section: T-cell Responses In Patients With Covid-19mentioning

confidence: 99%

Phenotypes and Functions of SARS-CoV-2-Reactive T Cells

Jung

Shin

2021

Molecules and Cells

Self Cite

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Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which is an ongoing pandemic disease. SARS-CoV-2specific CD4 + and CD8 + T-cell responses have been detected and characterized not only in COVID-19 patients and convalescents, but also unexposed individuals. Here, we review the phenotypes and functions of SARS-CoV-2-specific T cells in COVID-19 patients and the relationships between SARS-CoV-2-specific T-cell responses and COVID-19 severity. In addition, we describe the phenotypes and functions of SARS-CoV-2-specific memory T cells after recovery from COVID-19 and discuss the presence of SARS-CoV-2-reactive T cells in unexposed individuals and SARS-CoV-2-specific T-cell responses elicited by COVID-19 vaccines. A better understanding of T-cell responses is important for effective control of the current COVID-19 pandemic.

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

Cited by 202 publications

References 27 publications

Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection

Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection

SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8 ⁺ T cell activation in COVID-19 patients

Phenotypes and Functions of SARS-CoV-2-Reactive T Cells

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

Cited by 202 publications

References 27 publications

Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection

Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection

SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8 + T cell activation in COVID-19 patients

Phenotypes and Functions of SARS-CoV-2-Reactive T Cells

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SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8 ⁺ T cell activation in COVID-19 patients