- [NATURE COMMUNICATIONS] SARS-CoV-2 spike-specific nasal-resident CD49a+CD8+ memory T cells exert immediate effector functions w
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- 2025-01-06 10:12:14|
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[Title]
SARS-CoV-2 spike-specific nasal-resident CD49a+CD8+ memory T cells exert immediate effector functions with enhanced IFN-γ production
[Author]
Min-Seok Rha 1,2, Gyeongyeob Kim 1, Sol Lee1, Jihye Kim3, Yeonsu Jeong1, Chan Min Jung1, Hae Eun Noh1, Ji YunNoh4, Yong Min Kim 5,6, Hyung-Ju Cho1,2, Chang-Hoon Kim*1,2 & Eui-Cheol Shin* 3,7
1Department ofOtorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea.
2The AirwayMucus 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 author
[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-inducedmarkers 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 aswell 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.
SARS-CoV-2 spike-specific nasal-resident CD49a+CD8+ memory T cells exert immediate effector functions with enhanced IFN-γ production
[Author]
Min-Seok Rha 1,2, Gyeongyeob Kim 1, Sol Lee1, Jihye Kim3, Yeonsu Jeong1, Chan Min Jung1, Hae Eun Noh1, Ji YunNoh4, Yong Min Kim 5,6, Hyung-Ju Cho1,2, Chang-Hoon Kim*1,2 & Eui-Cheol Shin* 3,7
1Department ofOtorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea.
2The AirwayMucus 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 author
[Journal]
Nature Communications volume 15, Article number: 8355 (2024)[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-inducedmarkers 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 aswell 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.