# Function and regulation of brain resident memory T cells

> **NIH NIH K22** · DARTMOUTH COLLEGE · 2021 · $162,000

## Abstract

Project Summary/Abstract
Tissue resident memory T cells (TRM) are a newly define lineage of memory T cells that reside predominantly in
non-lymphoid tissues (NLT), rarely recirculate and are the main surveyors of NLT where they are poised to elicit
a potent and rapid response upon encountering reinfection. TRM are abundant in mouse and human and have
been described in the central nervous system (CNS). While T cells in the CNS have been implicated in both
health and disease, there persists a gap in knowledge regarding TRM regulation and function in the brain. The
applicant’s long-term goal is to understand immune cell function and surveillance in the CNS so that improved
therapeutic strategies can be developed against neurotropic infections and CNS autoimmunity. The objective of
this proposal is to establish a foundational understanding of TRM function and regulation in the CNS. This proposal
builds on the finding that expression of the inhibitory receptor, PD-1, is uniquely high on brain TRM and will test
the hypothesis that PD-1 signlaing functions to restrain the magnitude of TRM reactivation, protecting against
neurologic immunopathology. This hypothesis will be tested by integrating techniques examining transcriptional
and cellular changes as well as whole animal physiology. Aim 1 will define TRM reactivation, assess how PD-1
signaling modulates this, and evaluate the impact on activation of surrounding immune cells and animal
cognition. Aim 2 will investigate the impact of brain TRM reactivation on blood-brain barrier integrity, the influx of
circulating immune mediators (immune cells and antibody), and how PD-1 signaling may influence this. By
understanding the regulation and function of brain TRM, a foundational knowledge can be built upon to
contextualize the role of TRM in pathologic and protective settings. The applicant’s pre-doctoral training in virology
and innate neuroimmunology, fused with current post-doctoral training in tissue resident adaptive immunity
makes her well equipped to tackle large gaps in knowledge regarding neuro-immune interactions with a unique
perspective and armory of techniques. The applicant will continue to work with her mentor and take advantage
of opportunities at her current institution to develop skills necessary for successful transition to an independent
investigator. In summary, the K22 Career Transition Award will allow the applicant to attain her scientific and
career goals by providing a base of research and training to establish an independent NIH-funded program in
the field of neuroimmunology.

## Key facts

- **NIH application ID:** 9870360
- **Project number:** 1K22AI148508-01
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Pamela Rosato
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $162,000
- **Award type:** 1
- **Project period:** 2021-02-12 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9870360

## Citation

> US National Institutes of Health, RePORTER application 9870360, Function and regulation of brain resident memory T cells (1K22AI148508-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9870360. Licensed CC0.

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