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

在未暴露的口咽淋巴组织中鉴定对 SARS-CoV-2 具有功能特异性的驻留记忆 CD8+ T 细胞

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作者:Julia Niessl, Takuya Sekine, Joshua Lange, Viktoria Konya, Marianne Forkel, Jovana Maric, Anna Rao, Luca Mazzurana, Efthymia Kokkinou, Whitney Weigel, Sian Llewellyn-Lacey, Emma B Hodcroft, Annika C Karlsson, Johan Fehrm, Joar Sundman, David A Price, Jenny Mjösberg, Danielle Friberg, Marcus Buggert

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.

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