Clinical & translational immunology · 2026
Prolonged persistence of tissue-resident memory cells in the upper airway following SARS-CoV-2 infection and vaccination.
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Cha Hyunkyung, Won Jina, Kim Soo Min, Lim Suhyun, Kim Sujin, Jin Siyeon, Cho Sung Dong, Kim Hyun Jik
Аннотация
OBJECTIVES: Here, we characterised the diversity and persistence of immunological memory cells-particularly tissue-resident memory T (TRM) and B (BRM) cells-in the nasopharyngeal lymphoid tissues of healthy vaccinated (HV) individuals and those who experienced SARS-CoV-2 breakthrough infection (BR).
METHODS: Nasopharynx (NP) samples were obtained using brushing from HV and BR subjects. Immune cell populations were analysed using transcriptomic profiling and flow cytometry.
RESULTS: Transcriptomic profiling revealed that the NP of SARS-CoV-2-infected individuals exhibited distinctive signatures of lymphocyte-mediated immunity, underscoring its role as a key site for viral invasion and immune activation. Effector memory CD4+ and CD8+ T (TEM) cells, along with non-germinal center (GC) B cells, predominated in the NP. Although overall frequencies of memory T cells were comparable between HV and BR groups, CD4+ TEM and GC B cells were significantly enriched in the NP of BR individuals at least 1 year post infection. Notably, over 80% of CD4+ TEM and 40% of CD8+ TEM cells were TRM, and more than 30% of memory B cells exhibited a BRM phenotype. These populations of CD4+, CD8+ TRM and BRM persisted in the NP for over 2 years following SARS-CoV-2 infection or vaccination. In particular, CD4+ TRM cells were significantly more abundant and durably maintained in the NP mucosa of BR individuals.
CONCLUSION: Our findings identify the nasopharynx as a key site of long-lived immunological memory, marked by persistent TRM and BRM cells after SARS-CoV-2 exposure.
METHODS: Nasopharynx (NP) samples were obtained using brushing from HV and BR subjects. Immune cell populations were analysed using transcriptomic profiling and flow cytometry.
RESULTS: Transcriptomic profiling revealed that the NP of SARS-CoV-2-infected individuals exhibited distinctive signatures of lymphocyte-mediated immunity, underscoring its role as a key site for viral invasion and immune activation. Effector memory CD4+ and CD8+ T (TEM) cells, along with non-germinal center (GC) B cells, predominated in the NP. Although overall frequencies of memory T cells were comparable between HV and BR groups, CD4+ TEM and GC B cells were significantly enriched in the NP of BR individuals at least 1 year post infection. Notably, over 80% of CD4+ TEM and 40% of CD8+ TEM cells were TRM, and more than 30% of memory B cells exhibited a BRM phenotype. These populations of CD4+, CD8+ TRM and BRM persisted in the NP for over 2 years following SARS-CoV-2 infection or vaccination. In particular, CD4+ TRM cells were significantly more abundant and durably maintained in the NP mucosa of BR individuals.
CONCLUSION: Our findings identify the nasopharynx as a key site of long-lived immunological memory, marked by persistent TRM and BRM cells after SARS-CoV-2 exposure.