Identification of resident memory CD8+ T cells with functional specificity for SARS-CoV-2 in unexposed oropharyngeal lymphoid tissue


Science Immunology

Contributing to research themes:

Cross-reactive CD4+ T cells that recognize SARS-CoV-2 are more commonly detected in the peripheral blood of unexposed individuals compared to SARS-CoV-2-reactive CD8+ T cells. However, large numbers of memory CD8+ T cells reside in tissues, feasibly harboring localized SARS-CoV-2-specific immune responses. To test this idea, we performed a comprehensive functional and phenotypic analysis of virus-specific T cells in tonsils, a major lymphoid tissue site in the upper respiratory tract, and matched peripheral blood samples obtained from children and adults before the emergence of COVID-19. We found that SARS-CoV-2-specific memory CD4+ T cells could be found at similar frequencies in the tonsils and peripheral blood in unexposed individuals, whereas functional SARS-CoV-2-specific memory CD8+ T cells were almost only detectable in the tonsils. Tonsillar SARS-CoV-2-specific memory CD8+ T cells displayed a follicular homing and tissue-resident memory phenotype, similar to tonsillar Epstein-Barr virus-specific memory CD8+ T cells, but were functionally less potent than other virus-specific memory CD8+ T cell responses. The presence of pre-existing tissue-resident memory CD8+ T cells in unexposed individuals could potentially enable rapid sentinel immune responses against SARS-CoV-2.

Author list:

  1. Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.
  2. Division of Infection and Immunity, Cardiff University School of Medicine, University Hospital of Wales, Cardiff, UK.
  3. Biozentrum, University of Basel, Basel, Switzerland.
  4. ISPM, University of Bern, Bern, Switzerland.
  5. Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
  6. Department of Otorhinolaryngology, Karolinska University Hospital, Stockholm, Sweden.
  7. Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden.
  8. Systems Immunity Research Institute, Cardiff University School of Medicine, University Hospital of Wales, Cardiff, UK.
  9. Department of Surgical Sciences, Otorhinolaryngology and Head and Neck Surgery, Uppsala University, Uppsala, Sweden.

† Current affiliation: Roche Innovation Center, Basel, Switzerland.

‡ Current affiliation: BioNTech SE, Mainz, Germany.

* Corresponding author


Julia Niessl1,*, Takuya Sekine1, Joshua Lange1, Viktoria Konya1, Marianne Forkel1,†, Jovana Maric1, Anna Rao1,‡, Luca Mazzurana1, Efthymia Kokkinou1, Whitney Weigel1, Sian Llewellyn-Lacey2, Emma B. Hodcroft3,4, Annika C. Karlsson5, Johan Fehrm6,7, Joar Sundman6,7, David A. Price2,8, Jenny Mjösberg1, Danielle Friberg9, Marcus Buggert1,*