Leveraging Resident Memory T Cells to Fortify Oral Immunity

Resident memory T cells (TRM) durably survey barrier tissues for reinfection and orchestrate collaborative immune responses upon activation. Importantly, peptides derived from previously encountered viral infections can locally reactivate TRM. This biology may have convenient therapeutic ramifications for augmenting tissue-specific immunity. Yet, while TRM have been well-characterized in the gut, skin, and urogenital mucosa, the mouth remains a barrier tissue largely overlooked by T cell biologists. We asked whether TRM in the oral mucosa could be reactivated using virus-mimicking peptides, and if so, how that might impact oral immunity. This question was addressed using a novel prime-pull model for generating preternaturally abundant TRM in the mouths of SPF mice to manipulate and study. Oral TRM reactivation perpetuated a robust oral anti-pathogen state, including induction of key antiviral and interferon-stimulated genes, and recruitment of innate and adaptive cells into the oral mucosa. Oral peptide pre-exposure thwarted infection with an antigenically unrelated virus. Thus, mouth-resident T cells are amenable to local peptide reactivation, and their proinflammatory potential can be intentionally deployed to bolster oral immunity. Supported by T90 DE 022732 K99DE031014 OMIC Pilot Grant