# Regulation and Function of Oral Resident Memory T Cells

> **NIH NIH K99** · UNIVERSITY OF MINNESOTA · 2022 · $106,369

## Abstract

Project Summary/Abstract
Memory T cells chronicle an individual’s infectious past and afford protection to reinfection. Historically defined
in blood and subdivided based on their ability to access secondary lymphoid organs, an additional mechanism
of T cell immunosurveillance has more recently been described. Here, memory T cells forgo systemic
recirculation in exchange for durable residence in non-lymphoid tissues (NLT). Such tissue resident memory T
cell (TRM) provide a mechanism for stockpiling immunity within specific barrier compartments commonly exploited
by pathogens as portals of entry into the body. TRM function by rapidly intercepting invading pathogens and
orchestrating collaborative immune responses. Within NLT, T cell immunosurveillance is predominated by TRM
where they accelerate protection against reinfection, may be associated with tumor control, and may also
facilitate the persistence of certain allergic and autoimmune diseases. These observations have bolstered TRM
as major targets for vaccination. The therapeutic manipulation of TRM holds tremendous promise for the treatment
of organ-specific immunological disorders, autoimmunity, and solid cancers. 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. Considered amongst the most architecturally and biologically varied
tissue sites in the body, the mouth is continuously bombarded by myriad dietary and environmental antigens and
harbors diverse microbial communities. Moreover, the mouth and salivary glands can be colonized by bacterial,
fungal, and viral pathogens including herpes simplex virus and human papilloma virus. 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 suffered from a lack of animal models which would facilitate the generation of
sufficient oral TRM to manipulate and study. I have bridged this gap by developing a novel oral ‘prime-pull’
strategy, the first of its kind, for generating large quantities of tractable TRM in the oral mucosa. Leveraging this
innovative approach, I will address outstanding fundamental questions regarding oral TRM biology with
translational potential for human oral health. During the K99 phase, I will define the recruitment and retention
signals governing oral TRM with implications for depleting pathogenic subsets (Aim 1). Experiments spanning the
K99/R00 phases will investigate the consequences of oral TRM reactivation in shaping the microbial and
inflammatory landscape of the mouth with clinical relevance for recrudescent oral infections and oral cancer (Aim
2). Work conducted in the...

## Key facts

- **NIH application ID:** 10436381
- **Project number:** 5K99DE031014-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** James Michael Stolley
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $106,369
- **Award type:** 5
- **Project period:** 2021-07-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436381

## Citation

> US National Institutes of Health, RePORTER application 10436381, Regulation and Function of Oral Resident Memory T Cells (5K99DE031014-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10436381. Licensed CC0.

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