나민석 (연세대학교 의과대학)

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연세대학교 의과대학

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Nat. Commun., Sep 27 2024, 15 (1) 8355 | https://doi.org/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 Kim¹, Sol Lee¹, Jihye Kim³, Yeonsu Jeong¹, Chan Min Jung¹, Hae Eun Noh¹, Ji Yun Noh⁴, Yong Min Kim^5,6, Hyung-Ju Cho^1,2, Chang-Hoon Kim^1,2 & Eui-Cheol Shin^3,7

¹Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea.

²The Airway Mucus Institute, Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea.

³The Center for Viral Immunology, Korea Virus Research Institute, Institute for Basic Science, Daejeon, Republic of Korea.

⁴Division of Infectious Diseases, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea.

⁵Department of Otorhinolaryngology-Head and Neck Surgery, Research Institute for Medical Science, Chungnam National University School of Medicine, Daejeon, Republic of Korea.

⁶Department of Medical Science, Chungnam National University School of Medicine, Daejeon, Republic of Korea.

⁷Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.

Corresponding authors

Correspondence to Chang-Hoon Kim or Eui-Cheol Shin.

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.

논문정보

형식Research article
게재일2024년 09월 (BRIC 등록일 2024-09-30)
연구진국내 연구진
분야 의약학 > 면역의학

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