Signature of long-lived memory CD8+ T cells in acute SARS-CoV-2 infection

Sarah Adamo, Jan Michler, Yves Zurbuchen, Carlo Cervia, Patrick Taeschler, Miro E. Raeber, Simona Baghai Sain, Jakob Nilsson, Andreas E. Moor and Onur Boyman ()
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Sarah Adamo: University Hospital Zurich
Jan Michler: ETH Zurich
Yves Zurbuchen: University Hospital Zurich
Carlo Cervia: University Hospital Zurich
Patrick Taeschler: University Hospital Zurich
Miro E. Raeber: University Hospital Zurich
Simona Baghai Sain: ETH Zurich
Jakob Nilsson: University Hospital Zurich
Andreas E. Moor: ETH Zurich
Onur Boyman: University Hospital Zurich

Nature, 2022, vol. 602, issue 7895, 148-155

Abstract: Abstract Immunological memory is a hallmark of adaptive immunity and facilitates an accelerated and enhanced immune response upon re-infection with the same pathogen1,2. Since the outbreak of the ongoing COVID-19 pandemic, a key question has focused on which SARS-CoV-2-specific T cells stimulated during acute infection give rise to long-lived memory T cells3. Here, using spectral flow cytometry combined with cellular indexing of transcriptomes and T cell receptor sequencing, we longitudinally characterized individual SARS-CoV-2-specific CD8+ T cells of patients with COVID-19 from acute infection to 1 year into recovery and found a distinct signature identifying long-lived memory CD8+ T cells. SARS-CoV-2-specific memory CD8+ T cells persisting 1 year after acute infection express CD45RA, IL-7 receptor-α and T cell factor 1, but they maintain low expression of CCR7, thus resembling CD45RA+ effector memory T cells. Tracking individual clones of SARS-CoV-2-specific CD8+ T cells, we reveal that an interferon signature marks clones that give rise to long-lived cells, whereas prolonged proliferation and mechanistic target of rapamycin signalling are associated with clonal disappearance from the blood. Collectively, we describe a transcriptional signature that marks long-lived, circulating human memory CD8+ T cells following an acute viral infection.

Date: 2022
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DOI: 10.1038/s41586-021-04280-x

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