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

Min-Seok Rha, Gyeongyeob Kim, Sol Lee, Jihye Kim, Yeonsu Jeong, Chan Min Jung, Hae Eun Noh, Ji Yun Noh, Yong Min Kim, Hyung-Ju Cho, Chang-Hoon Kim () and Eui-Cheol Shin ()
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Min-Seok Rha: Yonsei University College of Medicine
Gyeongyeob Kim: Yonsei University College of Medicine
Sol Lee: Yonsei University College of Medicine
Jihye Kim: Institute for Basic Science
Yeonsu Jeong: Yonsei University College of Medicine
Chan Min Jung: Yonsei University College of Medicine
Hae Eun Noh: Yonsei University College of Medicine
Ji Yun Noh: Korea University College of Medicine
Yong Min Kim: Chungnam National University School of Medicine
Hyung-Ju Cho: Yonsei University College of Medicine
Chang-Hoon Kim: Yonsei University College of Medicine
Eui-Cheol Shin: Institute for Basic Science

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: 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+ 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.

Date: 2024
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DOI: 10.1038/s41467-024-52689-5

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