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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

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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

    Nat Commun


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

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



    AffiliationsAbstract

    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+ 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+ T cells. We detect multimer+CD8+ T cells with tissue-resident phenotypes in nasal tissue samples from vaccinees without infection as well as vaccinees with BTI. Multimer+CD8+ 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+CD8+ T cells-particularly the CD49a+ subset-exhibit immediate effector functions, including IFN-γ production. CITE-seq analysis of S-reactive AIM+CD8+ T cells confirms the enhanced effector function of the CD49a+ subset. These findings indicate that among individuals previously exposed to S antigen by vaccination or BTI, S-specific nasal-resident CD49a+CD8+ memory T cells can rapidly respond to SARS-CoV-2 during infection or reinfection.


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