2024/09/27 by Min‐Seok Rha, Gyeongyeob Kim, Sol Lee +9 · 1 voice · 1 citation
Medicine · Immunology and Microbiology · #SARS-CoV-2 and COVID-19 Research #COVID-19 Clinical Research Studies #Immunotherapy and Immune Responses
paper · pdf · doi:10.1038/s41467-024-52689-5
openalex publication_date 2024/09/27 · openalex created_date 2024/09/28 · openalex updated_date 2026/07/23
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. For infections that affect peripheral tissues it is better to promote immune responses in these tissues. Here the authors characterise nasal mucosal SARS-CoV-2-specific T cells in vaccinated individuals with or without breakthrough infection and show persistence and immediate effector function of these cells.