tetano
Editor, Senior Moderator
Nature
. 2021 Dec 7.
doi: 10.1038/s41586-021-04280-x. Online ahead of print.
Signature of long-lived memory CD8 [SUP]+[/SUP] T cells in acute SARS-CoV-2 infection
Sarah Adamo[SUP] 1 [/SUP], Jan Michler[SUP] 2 [/SUP], Yves Zurbuchen[SUP] 1 [/SUP], Carlo Cervia[SUP] 1 [/SUP], Patrick Taeschler[SUP] 1 [/SUP], Miro E Raeber[SUP] 1 [/SUP], Simona Baghai Sain[SUP] 2 [/SUP], Jakob Nilsson[SUP] 1 [/SUP], Andreas E Moor[SUP] 2 [/SUP], Onur Boyman[SUP] 3 4 [/SUP]
Affiliations
Abstract
Immunological memory is a hallmark of adaptive immunity and facilitates an accelerated and enhanced immune response upon re-infection with the same pathogen[SUP]1,2[/SUP]. Since the outbreak of the ongoing coronavirus disease 19 (COVID-19) pandemic, a key question has focused on which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells stimulated during acute infection give rise to long-lived memory T cells[SUP]3[/SUP]. Using spectral flow cytometry combined with cellular indexing of transcriptomes and T cell receptor (TCR) sequencing we longitudinally characterize individual SARS-CoV-2-specific CD8[SUP]+[/SUP] T cells of COVID-19 patients from acute infection to one year into recovery and find a distinct signature identifying long-lived memory CD8[SUP]+[/SUP] T cells. SARS-CoV-2-specific memory CD8[SUP]+[/SUP] T cells persisting one year after acute infection express CD45RA, interleukin-7 receptor α (CD127), and T cell factor-1 (TCF1), but they maintain low CCR7, thus resembling CD45RA[SUP]+[/SUP] effector-memory T (T[SUB]EMRA[/SUB]) cells. Tracking individual clones of SARS-CoV-2-specific CD8[SUP]+[/SUP] T cells, we reveal that an interferon signature marks clones giving rise to long-lived cells, whereas prolonged proliferation and mammalian target of rapamycin (mTOR) signaling are associated with clonal disappearance from the blood. Collectively, we describe a transcriptional signature that marks long-lived, circulating human memory CD8[SUP]+[/SUP] T cells following an acute virus infection.
. 2021 Dec 7.
doi: 10.1038/s41586-021-04280-x. Online ahead of print.
Signature of long-lived memory CD8 [SUP]+[/SUP] T cells in acute SARS-CoV-2 infection
Sarah Adamo[SUP] 1 [/SUP], Jan Michler[SUP] 2 [/SUP], Yves Zurbuchen[SUP] 1 [/SUP], Carlo Cervia[SUP] 1 [/SUP], Patrick Taeschler[SUP] 1 [/SUP], Miro E Raeber[SUP] 1 [/SUP], Simona Baghai Sain[SUP] 2 [/SUP], Jakob Nilsson[SUP] 1 [/SUP], Andreas E Moor[SUP] 2 [/SUP], Onur Boyman[SUP] 3 4 [/SUP]
Affiliations
- PMID: 34875673
- DOI: 10.1038/s41586-021-04280-x
Abstract
Immunological memory is a hallmark of adaptive immunity and facilitates an accelerated and enhanced immune response upon re-infection with the same pathogen[SUP]1,2[/SUP]. Since the outbreak of the ongoing coronavirus disease 19 (COVID-19) pandemic, a key question has focused on which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells stimulated during acute infection give rise to long-lived memory T cells[SUP]3[/SUP]. Using spectral flow cytometry combined with cellular indexing of transcriptomes and T cell receptor (TCR) sequencing we longitudinally characterize individual SARS-CoV-2-specific CD8[SUP]+[/SUP] T cells of COVID-19 patients from acute infection to one year into recovery and find a distinct signature identifying long-lived memory CD8[SUP]+[/SUP] T cells. SARS-CoV-2-specific memory CD8[SUP]+[/SUP] T cells persisting one year after acute infection express CD45RA, interleukin-7 receptor α (CD127), and T cell factor-1 (TCF1), but they maintain low CCR7, thus resembling CD45RA[SUP]+[/SUP] effector-memory T (T[SUB]EMRA[/SUB]) cells. Tracking individual clones of SARS-CoV-2-specific CD8[SUP]+[/SUP] T cells, we reveal that an interferon signature marks clones giving rise to long-lived cells, whereas prolonged proliferation and mammalian target of rapamycin (mTOR) signaling are associated with clonal disappearance from the blood. Collectively, we describe a transcriptional signature that marks long-lived, circulating human memory CD8[SUP]+[/SUP] T cells following an acute virus infection.