Generation and implications of oral resident memory T cells

Abstract

Abstract CD8+ tissue resident memory T cells (TRM) represent the predominant memory T cell population in many nonlymphoid tissues (NLT) where they are major contributors to localized immunosurveillance. TRM accelerate protection against reinfection, may be associated with tumor control, and may also facilitate the persistence of certain allergic and autoimmune diseases. While extensively studied in other mucosal sites, there is presently a fundamental void in our understanding of the ontogeny, function, and therapeutic implications of oral-mucosal TRM. Given their well-documented and critical functions in mediating barrier immunosurveillance in other NLT, oral TRM are likely to play a major role in antiviral immunity and oral immune homeostasis. TRM may also perpetuate chronic immune responses observed in periodontal disease and oral lichen planus. However, addressing their role in these clinically relevant settings has been mired by a lack of animal models for generating sufficient oral TRM to manipulate and study. Here we introduce a novel oral ‘prime-pull’ strategy for generating large quantities of tractable TRM of a defined antigen specificity within the oral mucosa. Leveraging this approach, we demonstrate that oral TRM 1) are abundant within mouse gingiva, 2) are intimately associated with salivary ducts of the tongue and buccal mucosa, and 3) can be locally reactivated to potentiate oral immunity. Ongoing work will further define the tissue-specific functions of oral TRM and describe new mechanisms by which oral immunity can be attenuated or augmented to achieve the desired clinical outcome.