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Protracted yet Coordinated Differentiation of Long-Lived SARS-CoV-2-Specific CD8⁺ T Cells during Convalescence.

ABSTRACT: CD8⁺ T cells can potentiate long-lived immunity against COVID-19. We screened longitudinally-sampled convalescent human donors against SARS-CoV-2 tetramers and identified a participant with an immunodominant response against residues 322 to 311 of nucleocapsid (Nuc_322-331), a peptide conserved in all variants of concern reported to date. We conducted 38-parameter cytometry by time of flight on tetramer-identified Nuc_322-331-specific CD8⁺ T cells and on CD4⁺ and CD8⁺ T cells recognizing the entire nucleocapsid and spike proteins, and took 32 serological measurements. We discovered a coordination of the Nuc_322-331-specific CD8⁺ T response with both the CD4⁺ T cell and Ab pillars of adaptive immunity. Over the approximately six month period of convalescence monitored, we observed a slow and progressive decrease in the activation state and polyfunctionality of Nuc_322-331-specific CD8⁺ T cells, accompanied by an increase in their lymph node-homing and homeostatic proliferation potential. These results suggest that following a typical case of mild COVID-19, SARS-CoV-2-specific CD8⁺ T cells not only persist but continuously differentiate in a coordinated fashion well into convalescence into a state characteristic of long-lived, self-renewing memory.

SUBMITTER: Ma T

PROVIDER: S-EPMC8763019 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Protracted yet Coordinated Differentiation of Long-Lived SARS-CoV-2-Specific CD8+ T Cells during Convalescence.

Ma Tongcui T Ryu Heeju H McGregor Matthew M Babcock Benjamin B Neidleman Jason J Xie Guorui G George Ashley F AF Frouard Julie J Murray Victoria V Gill Gurjot G Ghosn Eliver E Newell Evan W EW Lee Sulggi A SA Roan Nadia R NR

Journal of immunology (Baltimore, Md. : 1950) 20210813 5

CD8+ T cells can potentiate long-lived immunity against COVID-19. We screened longitudinally-sampled convalescent human donors against SARS-CoV-2 tetramers and identified a participant with an immunodominant response against residues 322 to 311 of nucleocapsid (Nuc322-331), a peptide conserved in all variants of concern reported to date. We conducted 38-parameter cytometry by time of flight on tetramer-identified Nuc322-331-specific CD8+ T cells and on ...[more]

PMID: 34389625

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Project description:BackgroundThe immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in COVID-19 patients has been extensively investigated. However, much less is known about the long-term effects of infection in patients and how it could affect the immune system and its capacity to respond to future perturbations.MethodsUsing a targeted single-cell multiomics approach, we have recently identified a prolonged anti-inflammatory gene expression signature in T and NK cells in type 1 diabetes patients treated with low-dose IL-2. Here, we investigated the dynamics of this signature in three independent cohorts of COVID-19 patients: (i) the Oxford COVID-19 Multi-omics Blood Atlas (COMBAT) dataset, a cross-sectional cohort including 77 COVID-19 patients and ten healthy donors; (ii) the INCOV dataset, consisting of 525 samples taken from 209 COVID-19 patients during and after infection; and (iii) a longitudinal dataset consisting of 269 whole-blood samples taken from 139 COVID-19 patients followed for a period of up to 7 months after the onset of symptoms using a bulk transcriptomic approach.ResultsWe discovered that SARS-CoV-2 infection leads to a prolonged alteration of the gene expression profile of circulating T, B and NK cells and monocytes. Some of the genes affected were the same as those present in the IL-2-induced anti-inflammatory gene expression signature but were regulated in the opposite direction, implying a pro-inflammatory status. The altered transcriptional profile was detected in COVID-19 patients for at least 2 months after the onset of the disease symptoms but was not observed in response to influenza infection or sepsis. Gene network analysis suggested a central role for the transcriptional factor NF-κB in the regulation of the observed transcriptional alterations.ConclusionsSARS-CoV-2 infection causes a prolonged increase in the pro-inflammatory transcriptional status that could predispose post-acute patients to the development of long-term health consequences, including autoimmune disease, reactivation of other viruses and disruption of the host immune system-microbiome ecosystem.

Dataset Information

Protracted yet Coordinated Differentiation of Long-Lived SARS-CoV-2-Specific CD8⁺ T Cells during Convalescence.

Publications

Protracted yet Coordinated Differentiation of Long-Lived SARS-CoV-2-Specific CD8<sup>+</sup> T Cells during Convalescence.

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