Peripheral and lung resident memory T cell responses against SARS-CoV-2

Judith Grau-Expósito, Nerea Sánchez-Gaona, Núria Massana, Marina Suppi, Antonio Astorga-Gamaza, David Perea, Joel Rosado, Anna Falcó, Cristina Kirkegaard, Ariadna Torrella, Bibiana Planas, Jordi Navarro, Paula Suanzes, Daniel Álvarez-Sierra, Alfonso Ayora, Irene Sansano, Juliana Esperalba, Cristina Andrés, Andrés Antón, Santiago Ramón y Cajal, Benito Almirante, Ricardo Pujol-Borrell, Vicenç Falcó, Joaquín Burgos, María J. Buzón () and Meritxell Genescà ()
Additional contact information
Judith Grau-Expósito: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
Nerea Sánchez-Gaona: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
Núria Massana: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
Marina Suppi: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
Antonio Astorga-Gamaza: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
David Perea: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
Joel Rosado: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
Anna Falcó: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
Cristina Kirkegaard: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
Ariadna Torrella: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
Bibiana Planas: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
Jordi Navarro: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
Paula Suanzes: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
Daniel Álvarez-Sierra: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
Alfonso Ayora: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
Irene Sansano: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
Juliana Esperalba: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
Cristina Andrés: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
Andrés Antón: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
Santiago Ramón y Cajal: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
Benito Almirante: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
Ricardo Pujol-Borrell: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
Vicenç Falcó: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
Joaquín Burgos: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
María J. Buzón: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus
Meritxell Genescà: Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: Abstract Resident memory T cells (TRM) positioned within the respiratory tract are probably required to limit SARS-CoV-2 spread and COVID-19. Importantly, TRM are mostly non-recirculating, which reduces the window of opportunity to examine these cells in the blood as they move to the lung parenchyma. Here, we identify circulating virus-specific T cell responses during acute infection with functional, migratory and apoptotic patterns modulated by viral proteins and associated with clinical outcome. Disease severity is associated predominantly with IFNγ and IL-4 responses, increased responses against S peptides and apoptosis, whereas non-hospitalized patients have increased IL-12p70 levels, degranulation in response to N peptides and SARS-CoV-2-specific CCR7+ T cells secreting IL-10. In convalescent patients, lung-TRM are frequently detected even 10 months after initial infection, in which contemporaneous blood does not reflect tissue-resident profiles. Our study highlights a balanced anti-inflammatory antiviral response associated with a better outcome and persisting TRM cells as important for future protection against SARS-CoV-2 infection.

Date: 2021
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DOI: 10.1038/s41467-021-23333-3

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