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-Roget, 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, Meritxell Genescà
Abstract
Abstract Resident memory T cells (T RM ) positioned within the respiratory tract are probably required to limit SARS-CoV-2 spread and COVID-19. Importantly, T RM 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-T RM 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 T RM cells as important for future protection against SARS-CoV-2 infection.