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

• Published in: Nature communications 2021-05, Vol.12 (1), p.1-17, Article 3010
• Main Authors: Grau-Expósito, Judith, Sánchez-Gaona, Nerea, Massana, Núria, Suppi, Marina, Astorga-Gamaza, Antonio, Perea, David, Rosado, Joel, Falcó, Anna, Kirkegaard, Cristina, Torrella, Ariadna, Planas, Bibiana, Navarro, Jordi, Suanzes, Paula, Álvarez-Sierra, Daniel, Ayora, Alfonso, Sansano, Irene, Esperalba, Juliana, Andrés, Cristina, Antón, Andrés, Ramón y Cajal, Santiago, Almirante, Benito, Pujol-Borrell, Ricardo, Falcó, Vicenç, Burgos, Joaquín, Buzón, María J., Genescà, Meritxell
• Format: Article
• Language: English
• Subjects: 13; 13/2; 13/21; 13/31; 13/51; 631/250/127; 631/250/2152/1566; 631/250/255/2514; 631/250/347; 692/699/255; Apoptosis; Biopsy; Blood; Blood circulation; CCR7 protein; Coronaviruses; COVID-19; Degranulation; Humanities and Social Sciences; Immunological memory; Infections; Inflammation; Interleukin 10; Interleukin 12; Interleukin 4; Lungs; Lymphocytes; Lymphocytes T; Memory cells; multidisciplinary; Parenchyma; Peptides; Respiratory tract; Science; Science (multidisciplinary); Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Viral diseases; Viral infections; Viruses; γ-Interferon
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-23333-3

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. Lung resident memory T (T RM ) cells are important for protection from viral infection in the lungs. Here the authors use paired lung biopsy material and blood to characterize T cell responses in patients with COVID-19 over time and find persistence of antiviral lung T RM cells that might be important to limit reinfection.