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; 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. American Association for the Advancement of Science 10.1126/sciimmunol.abk0894

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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.

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