Airway-resident T cells from unexposed individuals cross-recognize SARS-CoV-2


Nature Immunology

Contributing to research themes:

T cells can contribute to clearance of respiratory viruses that cause acute-resolving infections such as SARS-CoV-2, helping to provide long-lived protection against disease. Recent studies have suggested an additional role for T cells in resisting overt infection: pre-existing cross-reactive responses were preferentially enriched in healthcare workers who had abortive infections, and in household contacts protected from infection. We hypothesize that such early viral control would require pre-existing cross-reactive memory T cells already resident at the site of infection; such airway-resident responses have been shown to be critical for mediating protection after intranasal vaccination in a murine model of SARS-CoV3. Bronchoalveolar lavage samples from the lower respiratory tract of healthy donors obtained before the COVID-19 pandemic revealed airway-resident, SARS-CoV-2-cross-reactive T cells, which correlated with the strength of human seasonal coronavirus immunity. We therefore demonstrate the potential to harness functional airway-resident SARS-CoV-2-reactive T cells in next-generation mucosal vaccines.

Author list:


  1. Division of Infection and Immunity and Institute of Immunity and Transplantation, UCL, London, UK. 
  2. Department of Clinical Science, Liverpool School of Tropical Medicine, Liverpool, UK. 
  3. Institute of Child Health, London, UK. 
  4. Present address: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.


Mariana O. Diniz1, Elena Mitsi2, Leo Swadling1, Jamie Rylance2, Marina Johnson3, David Goldblatt3, Daniela Ferreira2,4 and Mala K. Maini1