Virus-specific resident memory T cell networks sustain immunity in human oral mucosa.

Publication date: Jun 11, 2026

Durable protection against viral infections relies on tissue-resident memory T (T) cells at pathogen entry sites. The oral cavity is a critical mucosal barrier frequently exposed to viral pathogens; however, the phenotypic characteristics and spatial organization of virus-specific T cells in the human oral mucosa remain poorly understood. This study aimed to define how virus-specific T cells maintain long-term residency in the oral mucosa and to identify cellular interactions supporting their persistence. We profiled predicted virus-specific T cells in the blood and oral mucosa of seven healthy individuals who recently recovered from SARS-CoV-2 infection. Single-cell RNA and T cell receptor sequencing, spatial transcriptomics, and immunofluorescence (IF) were used to define cell composition, localization, and interactions. Cytomegalovirus-specific T cells were predominantly CD4 effector memory T cells, whereas Epstein-Barr virus- and SARS-CoV-2-specific T cells were mainly CD8 T cells with cytotoxic features. Cell-cell communication analysis suggested that predicted virus-specific CD8 T cells were embedded in highly interactive signaling networks, receiving strong inputs from fibroblasts and dendritic cells. Spatial transcriptomics and IF confirmed close associations between CD8 T, fibroblasts, and dendritic cells. Predicted virus-specific CD8 T cells appear to play a prominent role in the human oral mucosa, where supportive communication networks with fibroblasts and dendritic cells likely contribute to their persistence and long-term survival at this critical barrier site.

Semantics

Original Article