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

Niessl, Julia, Sekine, Takuya, Lange, Joshua, Konya, Viktoria, Forkel, Marianne, Maric, Jovana, Rao, Anna, Mazzurana, Luca, Kokkinou, Efthymia, Weigel, Whitney, Llewellyn-Lacey, Sian, Hodcroft, Emma B., Karlsson, Annika C., Fehrm, Johan, Sundman, Joar, Price, David A., Mjösberg, Jenny, Friberg, Danielle and Buggert, Marcus 2021. Identification of resident memory CD8+ T cells with functional specificity for SARS-CoV-2 in unexposed oropharyngeal lymphoid tissue. Science Immunology 6 (64) , eabk0894. 10.1126/sciimmunol.abk0894

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Abstract

Cross-reactive CD4+ T cells that recognize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more commonly detected in the peripheral blood of unexposed individuals compared with 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 (coronavirus disease 2019). 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 preexisting tissue-resident memory CD8+ T cells in unexposed individuals could potentially enable rapid sentinel immune responses against SARS-CoV-2.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: This is an open-access article distributed under the terms of the Creative Commons Attribution license https://creativecommons.org/licenses/by/4.0/
Publisher: American Association for the Advancement of Science
ISSN: 2470-9468
Date of First Compliant Deposit: 21 January 2022
Date of Acceptance: 12 August 2021
Last Modified: 27 Jan 2022 11:58
URI: https://orca.cardiff.ac.uk/id/eprint/146834

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