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CD8+ T-Cell Signature in Acute SARS-CoV-2 Infection Identifies Memory Precursors
Adamo, S., Michler, J., Zurbuchen, Y. et al. Signature of long-lived memory CD8+ T cells in acute SARS-CoV-2 infection. Nature 602, 148–155 (2022). https://doi.org/10.1038/s41586-021-04280-x
In this study, Adamo et al. investigate the signature of SARS-CoV-2 specific long-lived memory CD8+ T cells using spectral flow cytometry combined with cellular indexing of transcriptomes and T-cell receptor (TCR) sequences in PCR confirmed COVID-19 patients.
SARS-CoV-2-specific CD8+ T cells were profiled directly ex vivo by single-cell RNA (scRNA) and TCR sequencing in PBMCs from 33 patients during acute COVID-19 as well as at six and 12 months after primary infection. SARS-CoV-2-specific CD8+ T cells were detected by using HLA-A*01:01, HLA-A*11:01, and HLA-A*24:02 MHC-I dCODE Dextramer® reagents.
scRNAseq analysis of the temporal phenotypic changes separated the SARS-CoV-2 specific CD8+ T cells into 12 distinct clusters based on gene expression (Fig. 1A. Clusters 1, 2, and 12 dominated the acute phase, while cluster 11 dominated the recovery phase (Fig. 1B). Clusters 1, 2, and 12 corresponded to cytotoxic, activated, and proliferating cells, while cluster 11 was enriched in IFN, TNF, and LT-α genes.
TCR sequencing revealed that the number of persistent clones decreased over time (Fig. 1C) and that those were enriched in genes involved in IFN-γ response, IFN-α response, and TNF signaling. Non-persisting cells were enriched in mTOR signaling genes and genes related to mitosis (Fig. 1D).
Fig.1: Temporal phenotypic transcriptional changes in SARS-CoV-2 CD8+ T cells. A) scRNASeq analysis of SARS-CoV-2 specific CD8+ T cells revealed 12 clusters with certain clusters dominating either acute or recovery phase. B) Clonotypes of SARS-CoV-2 specific CD8+ T cells determined by TCR sequencing. C) Distribution of persistent and non-persistent clones in acute phase. D) Gene expression in persistent and non-persistent SARS-CoV-2 CD8+ T cells.
- SARS-CoV-2 specific CD8+ T cells detected using dCODE Dextramer® reagents exhibited a Teffector phenotype during acute disease expressing genes related to cytotoxic, activated, and proliferating cells. During recovery, a progressive switch to a memory CD8+ T-cells phenotype with expression of genes related to IFN, TNF, and LT-α genes was observed in the SARS-CoV-2 specific CD8+ T cells
- Persisting SARS-CoV-2 CD8+ T-cell clones decreased over time but were enriched in genes involved in the IFN-γ response, IFN-α response, and TNF signaling