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Nat Commun . SARS-CoV-2 spike-specific nasal-resident CD49a+CD8+ memory T cells exert immediate effector functions with enhanced IFN-γ production

tetano

Editor, Senior Moderator
Nat Commun


. 2024 Sep 27;15(1):8355.
doi: 10.1038/s41467-024-52689-5. SARS-CoV-2 spike-specific nasal-resident CD49a[SUP]+[/SUP]CD8[SUP]+[/SUP] memory T cells exert immediate effector functions with enhanced IFN-γ production

Min-Seok Rha[SUP] 1 2 [/SUP], Gyeongyeob Kim[SUP] 1 [/SUP], Sol Lee[SUP] 1 [/SUP], Jihye Kim[SUP] 3 [/SUP], Yeonsu Jeong[SUP] 1 [/SUP], Chan Min Jung[SUP] 1 [/SUP], Hae Eun Noh[SUP] 1 [/SUP], Ji Yun Noh[SUP] 4 [/SUP], Yong Min Kim[SUP] 5 6 [/SUP], Hyung-Ju Cho[SUP] 1 2 [/SUP], Chang-Hoon Kim[SUP] 7 8 [/SUP], Eui-Cheol Shin[SUP] 9 10 [/SUP]



Affiliations
Abstract

Virus-specific nasal resident T cells are important for protection against subsequent infection with a similar virus. Here we examine the phenotypes and functions of SARS-CoV-2-specific T cells in the nasal mucosa of vaccinated individuals with breakthrough infection (BTI) or without infection. Nasal tissues are obtained from participants during sinus surgery. Analysis of activation-induced markers implicates that a considerable proportion of spike (S)-reactive nasal CD8[SUP]+[/SUP] T cells express CD103, a tissue-resident marker. MHC-I multimer staining is performed to analyze the ex vivo phenotype and function of SARS-CoV-2 S-specific CD8[SUP]+[/SUP] T cells. We detect multimer[SUP]+[/SUP]CD8[SUP]+[/SUP] T cells with tissue-resident phenotypes in nasal tissue samples from vaccinees without infection as well as vaccinees with BTI. Multimer[SUP]+[/SUP]CD8[SUP]+[/SUP] T cells remain present in nasal tissues over one year after the last exposure to S antigen, although the frequency decreases. Upon direct ex vivo stimulation with epitope peptides, nasal multimer[SUP]+[/SUP]CD8[SUP]+[/SUP] T cells-particularly the CD49a[SUP]+[/SUP] subset-exhibit immediate effector functions, including IFN-γ production. CITE-seq analysis of S-reactive AIM[SUP]+[/SUP]CD8[SUP]+[/SUP] T cells confirms the enhanced effector function of the CD49a[SUP]+[/SUP] subset. These findings indicate that among individuals previously exposed to S antigen by vaccination or BTI, S-specific nasal-resident CD49a[SUP]+[/SUP]CD8[SUP]+[/SUP] memory T cells can rapidly respond to SARS-CoV-2 during infection or reinfection.


 
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